Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
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protein kinase C alpha(PRKCA) protein kinase C alpha(PRKCA) Related Genes Homo sapiens
CHROMOSOME 17,
CYTOBAND 17q22-q23.2,
ENSEMBL_GENE_ID ENSG00000154229,
GENERIF_SUMMARY activation required for vitamin C-succinate induced apoptosis of HL-60 cells, Four residues located near the calcium binding site of PKC alpha are critical for activation and in vivo membrane translocation of the enzyme., Isoforms of protein kinase C and their distribution in human adrenal cortex and tumors, PKCalpha is required for ET-1-induced human myometrial cell growth, the first report of focal adhesion kinase and phosphatidylinositol 3-kinase-dependent PKC-alpha activation in bacterial invasion related to cytoskeletal reorganization, role in induction of metallproteinases 1 and 3 in fibroblasts by basic calcium phosphate crystals, Calcium-dependent involucrin expression is inversely regulated by protein kinase C (PKC)alpha and PKCdelta., PKC alpha expressed in human neutrophils can phosphorylate p47phox and induce both its translocation and NADPH oxidase activation as well as the binding of p47phox to the cytosolic fragment of p22phox., Data show that protein kinase Calpha mediates the effect of antiarrhythmic peptide on gap junction conductance., REVIEW, PKC alpha functions as a negative modulator of calcineurin-regulated retinoid X receptor responsive element-dependent transcription during T cell activation., A294G mutation of protein kinase C alpha does not detectably affect its biochemical properties in vitro or in vivo, and is at least rare in thyroid neoplasias, Cis activation of the basal promoter of the PKC alpha gene occurs through an activator protein-2-dependent, phorbol ester-responsive pathway, which suggests an autoregulatory manner of transcription in glioblastoma multiforme cells., Alpha-tocopherol decreases superoxide anion release in human monocytes under hyperglycemic conditions via inhibition of protein kinase C-alpha., Protein kinase C alpha plays an important role in activating store-operated Ca2+ channels (SOC) in human mesangial cells, Activation of PKCalpha stabilizes F-actin and thereby opposes the effect of PKCepsilon on membrane remodeling in T84 cells., Our findings present original data that PKCalpha is the isoform specifically involved in the proliferation of primary human osteoblasts., greater increase of PKCalpha translocation after PMA treatment in breast cancer erythrocytes compared to controls was observed, Il-2 increased protein kinase C alpha expression, but polysaccharide K decreased it., the direct PKC-dependent activation of the amyloid protein precursor secretory pathway is compromised by reduced PKCalpha expression and a specific role of this isoform in these mechanisms, PKCalpha may regulate Ets1 activity in invasive breast cancer cells, PKC alpha plays a necessary role in mediating calcium-induced differentiation. Failure to regulate PKC alpha in SCC4 carcinoma cells may underlie at least part of the failure of calcium to promote differentiation in these cells., Filamin A was identified as a direct binding partner of protein kinase Calpha; two binding sites were identified on filamin A; a Ca2+ and phospholipid-dependent association of the regulatory domain of protein kinase C with these sites was revealed., PKCalpha is involved in the regulation of Ca2+-induced platelet aggregation., data demonstrate a pathway of Rho activation involving protein kinase c alpha-dependent phosphorylation of p115Rho guanine exchange factor, The novel varepsilon and eta and atypical zeta, but not the conventional alpha and beta and the novel delta PKCs, may be involved in the signaling pathways involved in thrombin-induced human platelet P-selectin expression, Protein kinase C promotes apoptosis in LNCaP prostate cancer cells through activation of p38 MAPK and inhibition of the Akt survival pathway, protein kinase C alpha associates with phospholipase D1 and enhances basal phospholipase D activity in a protein phosphorylation-independent manner in melanoma cells, which contributes to the cell's high invasive potential., Protein kinase C alpha negatively regulates cell spreading and motility in breast cancer cells., PKC alpha phosphorylates diacylglycerol kinase zeta in cells, and this phosphorylation inhibits its kinase activity to remove cellular diacylglycerol, thereby affecting cell growth., Loss of protein kinase Calpha expression may enhance the tumorigenic potential of Gli1 in basal cell carcinoma., protein kinase C alpha signaling is activated by apolipoprotein A-I, and it has a role in phosphorylation and stabilization of ATP binding cassette transporter A1 for the high density lipoprotein assembly, the affinity of isolated C1A and C1B domains of PKCalpha and PKCgamma for soluble and membrane-incorporated DAG and phorbol ester were measured by isothermal calorimetry and surface plasmon resonance in order to compare activation mechanisms, there is an impairment of degradation of protein kinase c alpha in huntington disease 150q cells that is connected with the sequestration of proteasome on mutant huntingtin aggregates, PKCA acts upstream of PKCtheta to activate IkappaB kinase and NF-kappaB in T-lymphocytes., PKCalpha and betaII have roles in the regulation of membrane recycling, in gastric cancer, protein translocation of PLCgamma2 and PKCalpha is critical event in the process of apoptosis induction., PKC-alpha and PKC-epsilon act cooperatively in regulating JNK activation in response to PMA, Only PKC-alpha is involved in the signal transduction cascade leading to neutrophil transepithelial migration., PKC alpha is a critical regulatory element that is required for efficient regulatory volume decrease in HeLa cells, PKCalpha-S100C/A11-mediated pathway is involved in and essential for the growth inhibition of normal human keratinocytes cells by TGFbeta1., PKD activation plays a central role in NT peptide secretion; upstream regulators of PKD include PKC-alpha and -delta and Rho/ROK, There was expression of protein kinase C alpha in abnormal muscle fibers. Protein kinase C isoforms may play a role in the pathogenesis of myofibrillar myopathy., PKCA has a major role in cytoskeleton-dependent avidity modulation of ALCAM., protein kinase C alpha, iota, and theta binding to L-selectin cytoplasmic domain is modulated by receptor phosphorylation, Results suggest that the involvement of protein kinase C alpha in carbachol-induced soluble amyloid precursor protein (sAPPalpha) release is negligible, but PKC epsilon may be important in coupling cholinergic receptors with APP metabolism., phosphorylation of LRP by PKCalpha modulates the endocytic and signaling function of LRP by modifying its association with adaptor proteins, autophosphorylation of PKCalpha limits its sensitivity to DAG; kinase inhibitors augment the DAG sensitivity of PKCalpha by destabilizing the closed conformation, Use of PKC agonists and isozyme-specific pseudosubstrate peptide antagonists suggested a role for PKCalpha and -epsilon in VEGF-mediated DAF up-regulation, mediating A cytoprotective pathway in ECs., Results propose a new mechanism by which lithium indirectly inhibits glycogen synthase kinase-3beta via phosphatidylinositol 3 kinase-dependent activation of protein kinase C alpha., We analyzed the dependence of the expression of some selected protein kinase C isoenzymes on the availability and/or action of androgens., PKC-alpha-mediated NG2 phosphorylation at Thr(2256) is a key step for initiating cell polarization and motility, central role of PKC isoforms and the negative regulatory function of c-Src in the control of stromelysin 3 expression, Ets1 serves as an effector for PKCalpha to fulfil certain functions in cancer ce, we used publicly available gene expression array data to further understand PKC-a-associated gene expression profiles in NSCLC, protein kinase Calpha transcriptional repression via Sp1 by wild type p53 is involved in inhibition of multidrug resistance 1 P-glycoprotein phosphorylation, colocalizes with virus particles and is required for Respiratory syncytial virus (RSV) fusion to the cell membrane of bronchial epithelial cells, diacylglycerol-responsive PKC isoforms differentially influence CaR agonist-induced release of Ca2+ from internal stores, Calpha activation and phosphorylation of syntaxin 4 and Munc18c are required for the cell surface expression of P-selectin and the consequent binding of neutrophils to endothelial cells., there is a complex interplay between PKCalpha, Syk, and Src involving physical interaction, phosphorylation, translocation within the cell, and functional activity regulation, protein kinase C has a role in chitosan glutamate-mediated tight junction disruption, Epidermal and hepatocyte growth factors, but not keratinocyte growth factor, modulate protein kinase Calpha translocation to the plasma membrane, two fatty acids inhibited the phorbol 12-myristate 13-acetate (PMA)-induced plasma membrane translocation of protein kinase C (PKC)-alpha and -epsilon, Results demonstrate that a branched signaling pathway involving MEK, ERK, PKCepsilon, PKCalpha, and caveolin-1 regulates collagen expression in normal lung tissue and is perturbed during fibrosis., NAG-1 expression is up-regulated by TPA in LNCaP cells through a PKC-dependent pathway involving the activation of NF-kappa B, Inhibition of the oxidative burst, i.e., cellular desensitization, was clearly reversed in cells overexpressing PKC alpha, pointing to PKC alpha as the major transmitter in eliciting the oxidative burst in monocytes/macrophages., PKCalpha is specifically required for TPA-induced ERK(MAPK) signaling to trigger gene expressions of p15(INK4b) and p16(INK4a) leading to HepG2 growth inhibition, PRKCA-dependent PRKD1 activation modulates ERK signal pathway and endothelial cell proliferation by vascular endothelial growth factor A., PKCalpha C1A-C2 interdomain interactions have a role in lipid-mediated PKCalpha activation, The data do not support a strong association between single nucleotide polymorphism of PRKCA and spina bifida risk., PKCalpha stimulates NO production in endothelial cells and plays a role in regulation of blood flow in vivo., Results identify targets in RLIP76 for phosphorylation by protein kinase C alpha, which may act as substrates for differential transport of doxorubicin., PKC stimulation upregulates neuron-specific ELAV (nELAV) proteins (HuB, HuC, and HuD), and induces nELAV proteins to colocalize with the translocated PKCalpha isozyme on the cytoskeleton, with a concomitant increase of nELAV threonine phosphorylation., Ca2+-activated PKCalpha and its isolated C2 domain localize exclusively to the plasma membrane, PKCalpha expression may be modulated by Elk-1 and MZF-1 at the transcriptional level., Thrombin is able to induce activation of caspases 3 and 9 in human platelets and significantly increases the amount in the cytoskeleton of the active forms of both caspases and the procaspases 3 and 9., protein phosphorylation and dephosphorylation via PKC and the corresponding protein phosphatases contribute to phosphatidylserine exposure and erythrocyte shrinkage after energy depletion, increased expression of PKC-alpha and -betaI leads to increased total classical PKC kinase activity; increased activity of the isoenzymes plays a role in accelerated growth of TCC. In carcinoma tissue, PKC expression and activity are under strict control., Data show that protein kinase C-alpha activation in endothelial cells leads to upregulation of sphingosine kinase-1 expression and activity, which is critically involved in the mechanism of endothelial cell migration., Inhibition of Protein Kinase C represents a mechanism by which high tyrosine kinase activity can enhance cellular Ca(2+) transients and thus exert profound effects on the proliferation, apoptosis and chemotaxis of leukemic cells., PKC alpha mmodulates Bcl2 phosphorylation and is relevant to chemoresistance in acute myeloid leukemia, effect of insulin is dependent on activation of PKCalpha and/or PKCbeta, and these insulin signals may interfere with the dynamic assembly/disassembly and/or distribution of F-actin, which is required for the phagocytosis process, PKCalpha activation is a critical step in androgen receptor nuclear exclusion by melatonin., In conclusion, although CDCA and UDCA activate different PKC isoforms, PKCalpha plays a major role in the bile acid-induced inhibition of cAMP synthesis in fibroblasts., PKC regulates sequestration of recycling molecules into this compartment, the pericentrion; PKC acted distal to the site of internalization of endocytic cargo, Incubation of podocytes with membranous glomerulonephritis sera determined strong upregulation of pPKC-alpha/beta that was reverted by pre-incubation with clusterin, The overexpression of protein kinase CK2alpha is closely related to the formation and development of laryngeal squamous cell carcinoma., RLIP76-/- mouse embryonic fibroblasts were resistant to PKCalpha-depletion mediated growth inhibition, as well as to the PKCalpha-dependent mitogen, phorbol 12-myristate 13-acetate (PMA)., WISP-2/CCN5 is a novel signaling molecule that critically participates in the mitogenic action of PMA on noninvasive, WISP-2/CCN5-positive breast tumor cells through PKCalpha-dependent, multiple molecular signal transduction pathways., We conclude that compound 48/80 is an effective activator of PI 3-kinase dependent pathways, leading to the activation of effectors including PKB/Akt, p70(S6K) and PKCalpha., Our data suggest that PKCalpha, but not PKCbeta, is the predominant cPKC isoenzyme required for cPLA(2) protein phosphorylation and maximal induction of cPLA(2) enzymatic activity upon activation of human monocytes., PCK-alpha activation in keratinocytes is a crucial event orchestrating cutaneous neutrophil responses., These results show for the first time that IP6 represses telomerase activity in prostate cancer cells by posttranslational modification of TERT via the deactivation of Akt and PKCalpha., NT uses PKC-dependent pathways to modulate GSK-3, which may play a role in the NT regulation of intestinal cell growth, a functional contribution of PKCalpha to tamoxifen resistant growth of human breast cancer cells, alpha-PKC and beta-PKC are required for optimal O(2)(-) generation, but play different roles in Ca2+ signaling for phagocytic responses such as O(2)(-) generation, Data suggest that MCF-7 cell proliferation or the anti-cancer action of doxorubicin and vinblastine on breast cancer cells is independent of PKC-alpha., Galphaq activation of TRPC6 signals the activation of PKCalpha, and thereby induces RhoA activity and endothelial cell contraction, These results suggest that different PKC isoforms may exert ontogenetic-specific functions in erythropoiesis and that modulation of PKCalpha might affect the activity of (A)gamma-promoter-driven reporters., Ras is able to promote monocyte lineage selection via PKC., Conventional PKC isoforms, especially PKCalpha, mediate feedback inhibition of G-protein-coupled receptor -induced EGFR transactivation., These data suggest that an intracellular calcium store independent PKC-Sp1 signaling pathway induces early keratinocyte differentiation through upregulation of TSG101., "PKCalpha-NF- kappaB"-dependent cascade is involved in the signaling leading to phorbol myristate acetate-induced matrix metalloproteinase-9 expression in the lung epithelium, These data demonstrate that IGF-I induces COX-2 expression in human ovarian cancer cells, which is mediated by three parallel signaling cascades--PI3K, MAPK, and PKC pathways that differentially regulate COX-2 expression., AP-1 may participate in the signal transduction of PKC-triggered expression of IL-5 in allergic rhinitis T lymphocytes., the cell fate commitment of CD14(+)monocytes towards MDMs or MoDCs appears to be steered by the selective activation of PKCalpha or PKCbeta(I), respectively., Protein Kinase C alpha mRNA was significantly increased in human hepatocellur carcinomas as compared to corresponding non-cancerous liver tissues., STAT3 and PKC differentially regulate telomerase activity during megakaryocytic differentiation of K562 cells., HER2 overexpression in HER2 2+ carcinomas is associated with neither an increase in gene transcription nor a deregulation in the ubiquitin-dependent pathways, but instead seems to be regulated by protein kinase Calpha (PKCalpha) activity., Determination of PKC-alpha levels/activity in leukaemia seems to be relevant when choosing efficient chemotherapy protocols based on the use of apoptosis-inducing anticancer drugs., Differential phosphorylation of NG2 proteoglycan by ERK and PKCA helps balance cell proliferation and cell movement., analysis of direct binding and activation of PKCalpha and PKCdelta by steroid hormones and the molecular mechanisms involved, PKC-alpha is the predominant conventional PKC present in the human coronary and skeletal microcirculation, PKC alpha, rather than other protein kinase C isoforms, participates in lysophosphatidic acid-induced NF-kappa B activation and urokinase upregulation in ovarian cancer cells., Hemoglobin promptly and markedly modified the levels of expression of both calcium-dependent PKCalpha and calcium-independent PKCzeta., Ginkgo Biloba extract may decrease the activation of the PKCalpha in the inflammatory cells and thereby decrease the IL-5 level in induced sputum of asthmatic patients., The protein kinase C (PKC) inhibitor and apoptotic inducer staurosporine switches the production of Bcl-x towards the x(S) mRNA isoform in 293 cells., These results suggest that the PKCalpha isoform is an important regulator of cell migration in response to agricultural dust exposure., Data show that expression of DMPK-CUG-repeat RNA results in hyperphosphorylation and stabilization of CUGBP1, and suggest that inappropriate activation of the PKC pathway contributes to the pathogenic effects of a noncoding RNA., findings provide the first evidence that stimulation of P-selectin surface expression via PKCalpha-dependent PKD2 activation could be an important mechanism in the early onset of AII-initiated endothelial adhesiveness., Study shows that activation of protein kinase C-alpha (PKC-alpha) phosphorylated and down-regulated LRP expression., Protein kinase C alpha promotes angiogenic activity of human endothelial cells via induction of vascular endothelial growth factor., Ro3582 inhibits cell proliferation and activates bone morphogenetic protein/Smad signaling via a Ras and PKC alpha pathway in breast epithelial cells., discrete PKCs trigger distinctive responses when activated in different phases of the cell cycle via a common mechanism that involves p21 Cip1 up-regulation., Moraxella catarrhalis infection activates protein kinase C and its isoforms alpha, epsilon and theta, which differentially regulate interleukin-8 transcription in human pulmonary epithelial cells., RXR ligands rapidly inhibit high-glucose-induced oxidative stress by antagonizing high-glucose-induced PKC activation, and cytoplasmic RXRalpha is implicated in this regulation, In pancreatic tumor cells calcium-dependent PKC-alpha mediates TGF-beta-induced transcriptional downregulation of PTEN, and this pathway promotes cell migration in a SMAD4-null environment., Data show that NG2 and integrin alpha4 oppositely regulate anoikis in fibroblasts, and that NG2 and integrin alpha4 regulate FAK phosphorylation by PKCalpha-dependent and -independent pathways, respectively., Overexpression of protein kinase Calpha mRNA is associated with gastric carcinoma, modulation of PKC may have therapeutic potential in the prevention of smoke-related lung injury, Protein kinase C alpha modulates liver X receptor alpha transactivation., A novel regulatory signaling mechanism of transcriptional control in which the LHR is derepressed through PKCalpha/ERK-mediated Sp1 phosphorylation, causing the release of HDAC1/mSin3A complex from the promoter., Thus, survivin, Smac, and PKC alpha might play important roles in the inhibition of apoptosis by FGF-2 in human small cell lung cancer cells., IGF-II/mannose-6-phosphate receptor signaling induced cell hypertrophy and atrial natriuretic peptide/BNP expression via Galphaq interaction and protein kinase C-alpha/CaMKII activation in H9c2 cardiomyoblast cells., PKP2 knockdown is accompanied by increased phosphorylation of PKC substrates, raising the possibility that global alterations in PKC signaling may contribute to pathogenesis of congenital defects caused by PKP2 deficiency., These results suggest a significant role of PKCalpha and downstream actin filament activity during the fungal invasion into human brain microvascular endothelial cells., TRPV1 mediates heat shock-induced MMP-1 expression via calcium-dependent PKCalpha signaling in HaCaT cells, A 46kDa variant of ERalpha increased in abundance in the cell membrane within 20 minutes of estradiol treatment suggesting that ERalpha mediated the estradiol non-genomic effects on PKCA through the formation of a membrane-associated signalling complex., A novel interferon-independent pathway involving protein kinase C (PKC)-alpha activation, upstream of p38 and c-jun N-terminal kinase, is responsible for poly (I, Akt-mediated phosphorylation modulates eNOS uncoupling and greatly increases O(2)* generation from the enzyme at low Ca(2+) concentrations, and PKCalpha-mediated phosphorylation alters the sensitivity of the enzyme to other negative regulatory signals., The expression of P-cadherin (a marker of proliferating keratinocytes) was regulated by all of the examined protein kinase C isoenzymes, also in an antagonistic manner (inhibited by cPKCalpha/nPKCdelta and stimulated by cPKCbeta/nPKCepsilon)., phosphorylation of FXR induced by PKCalpha directly modulates the ability of agonists to activate FXR, PDGFR-mediated phosphorylation at this site is dependent on PKCalpha, a conventional PKC isoform implicated previously in disruption of adherens junctions., The direct interaction of PI3Kgamma with PKCalpha forms a discrete regulatory module of N-formylmethionyl-leucyl-phenylalanine-dependent reactive oxygen species production in neutrophils., findings shed light on post-transcriptional regulation of HSP70 expression, suggesting a molecular cascade involving PKC/HuR/HSP70- that possibly represents an early event in the cellular response to oxidative stress in SH-SY5Y human neuroblastoma cells, Findings support a model in which activation of PKCalpha downregulates ATM protein and delays tumor growth in prostate cancer cells., An investigation of the marine compound spongistatin 1 links the inhibition of Pkca translocation to nonmitotic effects of tubulin antagonism in angiogenesis., ezrin is regulated during osteosarcoma metastasis by PKC, These results provide evidence for the existence of a cAMP-dependent but PKA-independent pathway in mediating the endothelial cell-conditioned medium-induced aldosterone release and the significant influence of more than one signaling mechanism., Protein kinase Calpha levels are elevated in the pregnant myometrium suggesting the involvement of protein kinase Calpha in regulation of human uterine contraction., ANG II inhibited hOAT1 activity through activation of PKCalpha, which led to the redistribution of the transporter from the cell surface to the intracellular compartments., These results demonstrated that in A549 cells, activation of p50/p65 heterodimer through sequential activation of PKC alpha-JNK-NIK-IKK beta-NF-kappaB was required for IL-1 beta-induced uPA expression associated with migration of tumor cells., Evidence suggesting that SPHK enhances migration of ML-1 cells by an autocrine mechanism and that the S1P-evoked migration is dependent on protein kinase C alpha, ERK1/2, and SPHK., p73 is able to induce cell cycle arrest independently of its amino-terminal transactivation domain, whereas this domain is crucial for p73 proapoptotic functions., EGFR signals to mTOR through PKC and independently of Akt in glioma, Protein kinase C alpha (PKCalpha) regulates growth and invasion of endometrial cancer cells., PKCalpha positively regulates multidrug resistance(MDR) in a stomach cancer cell line and inhibition of PKCalpha can partially attenuate MDR in human gastric cancer cells., A functional polymorphism that impairs the activity of PHLPP2 and correlates with elevated Akt phosphorylation and increased PKC levels, was identified., PKC(alpha) and PKC(epsilon) differentially regulate Legionella pneumophila-induced GM-CSF, PKCalpha activation is both necessary and sufficient to trigger irreversible growth arrest during human epidermal keratinocyte differentiation., N-cadherin cleavage is regulated by a PKC-alpha-metalloproteinase ADAM-10 cascade in glioblastoma (GBM) cells and may be involved in mediating GBM cell migration., These results suggest that LeY oligosaccharide acts as a signal molecule to modulate diacylglycerol/PKC signaling pathway., PKCA-responsive polymeric carrier, Results show that the expression of PKCalpha in proliferating intestinal epithelial cells is repressed both in vitro and in vivo by the SOX9 transcription factor., ESI-MS analysis and cellular expression of PB1-F2 mutants identified the positions Ser-35 as the major and the Thr-27 as an alternative PKC phosphorylation site., PRKCA is a pleiotropic locus that is associated with both BMI and asthma and that has been identified via linkage analysis of BMI in a Costa Rican population with asthma., Mutation of protein kinase C phosphorylation site S1076 on alpha-subunits affects BK(Ca) channel activity., Data imply that targeting CAV1 and/or PKCalpha may allow the development of new molecular therapeutic strategies to improve the treatment outcome for patients with ESFT., The functional analysis on the relationship between CCh-induced calcium response and endogenous PKCalpha expression might be helpful to predict the development of melanoma., The cascade of events initiated by hog dust exposure is mediated by PKC-alpha/-epsilon and ultimately results in the release of TNF-alpha., molecular mechanism for the regulation of FR recycling through PKC, PKCalpha- and PKCepsilon-mediated phosphorylation of cMyBP-C and cTnI as well as cTnT decrease myofilament Ca2+ sensitivity and may thereby reduce contractility and enhance relaxation of human myocardium., Overexpression of Protein kinase C alpha is associated with endometrial cancer., YadA and invasin of Yersinia pseudotuberculosis both trigger signal transduction pathways during integrin-mediated phagocytosis into epithelial cells, which lead to the activation of Akt, PLC-gamma1, PKCalpha and -beta downstream of PI3 kinase., PKC activation can up-regulate CD44 expression by phosphorylation in human erythrocytes., SH2D4A inhibited cell proliferation by suppression of the ERalpha/PLC-gamma/PKC signaling pathway., We conclude that, although we have obtained convergent lines of evidence implicating both rare and common schizophrenia risk variants at PRKCA, none of these is individually compelling, Data show that PKCalpha was slightly elevated in HUVECs exposed to UKF-NB-4., Data show that stimulation of HIF-1alpha transcription by the ND6 mutation was mediated by overproduction of reactive oxygen species (ROS) and subsequent activation of phosphatidylinositol 3-kinase (PI3K)-Akt and protein kinase C (PKC) signaling pathways., Modulation of PKCalpha by histamine receptors may be important in regulating cholangiocarcinoma growth., Results show that IGF-IR can inhibit PKC-alpha gene transcription and thereby block the synthesis of PMA-regulated MMPs, suggesting that within the same cells, IGF-IR can act as both a positive and negative regulator of MMP expression and function., PMA-responsive cPKC isoforms (alpha, beta and gamma) play a key role in negative regulation of CD98 signalling and homotypic aggregation, Data demonstrate that PKC-alpha is induced by several MyD88-dependent TLR/IL-1R ligands and regulates cytokine expression in human and murine DC., These results suggest that PKC(alpha) affects cell cycle progression and proliferation in human RPE cells through the downregulation of p27(kip1)., The results demonstrate that pathogenic mycobacteria recognize and then inhibit PKCalpha via the action of PknG to circumvent phagocytosis and the hostile environment of macrophages., The anti-angiogenic effect of PPARgamma agonists is due, at least in part, to an interference with the VEGF-stimulated PKCalpha-mediated activation of CREB and the related expression of COX-2., Am80 inhibits surface CXCR4 expression and SDF-1-induced chemotaxis by the acceleration of CXCR4 internalization via activation of conventional PKC, Mda-9/syntenin acts as a molecular adaptor linking PKCalpha and FAK activation in a pathway of FN adhesion by human cancer cells., Data suggest that phosphorylation of S26 is the primary mechanism through which PKCalpha modulates cardiac stiffness., PKC-alpha plays an important role in melanoma cell migration, TNF-alpha induces MMP-9 expression via the TNFR1/TRAF2/PKCalpha-dependent JNK1/2/c-Jun and c-Src/EGFR/PI3K/Akt pathways., risk of preterm delivery that is associated with tag polymorphisms in genes that regulate the inflammatory response is modified by an environmental exposure such as bacterial vaginosis, Phosphorylation of S(695) by PKC or introducing a phosphomimetic aspartate at this position (S(695)D) renders BK channels insensitive to the stimulatory effect of PKG or PKA., PKCalpha is a marker for poor prognosis of breast cancer, Increased expressions of PKCalpha and cyclin D1 might be involved in the pathogenesis of abnormal proliferation of pulmonary artery smooth muscle cells in smokers with normal lung function and smokers with mild to moderate COPD., PKCalpha is involved in reduction of nephrin surface expression; activation of PKCalpha is a pathomechanistic key event during the development of diabetic nephropathy, Overexpression of IGF-IR and PKC may play an important role in the carcinogenesis and development of laryngeal squamous cell carcinoma., promotes the proliferation of human airway smooth muscle cells sensitized with atopic asthmatic serum via up-regulation of cyclin D1 expression, Activation of PKCalpha by phorbol esters or thymeleatoxin causes a transient increase of arginine transport through system y(+), referable to the induction of SLC7A2 mRNAs and to the increased expression of CAT2 transporters., PKCalpha and ERK pathways play an important role in activating miR-101 expression, reducing PRC2 complex and H3K27me3 levels in HepG2 hepatoma cells., The application of flavonoids to prevent the migration/invasion of glioblastoma cells through blocking PKCalpha/ERK/NF-kappaB activation is demonstrated., Three different isotypes of protein kinase C, i.e. PKC-alpha, PKC-eta and PKC-theta, were found to be regulated and translocated in opposite directions upon apoptosis induction., Activation of PKC reduced expression of NOS3 in endothelial cells treated with oleic acid., These results confirm the novel possibility that PKCalpha is a direct substrate of Erk1/2 in neuronal cells and help link two important signaling molecules that regulate maturation and protection of hippocampal neurons as well as many other cell types., intracellular Francisella tularensis novicida triggers temporal and early activation of Ras through the SOS2/GrB2/PKCalpha/PKCbetaI quaternary complex; Ras signalling by intracellular F. tularensis is essential for intracellular proliferation in the cytosol, The results suggest ERCC1 and PKCalpha might be correlated with the development of NSCLC. ERCC1 might be related to prognosis of non-small cell lung cancer., Production of the PKCalpha C-terminal fragment in ischemic hearts occurs via a receptor-independent mechanism, these results suggest that PKC-alpha is a candidate for PDK-2 in T cells upon TCR stimulation., Results provide evidence for both physical and functional interactions between the PKC and Fbw7 families, and yield insights into the isoform-specific regulation of Fbw7alpha., Results reveal novel signalling cross-talk, whereby RACK1 mediates PKC-dependent activation of PDE4D5 in the particulate fraction of HEK-293 cells in response to elevations in intracellular cAMP., PKC-dependent phosphorylation of the alpha4 subunit plays a significant role in enhancing the cell surface stability and activity of GABA(A)R subtypes that mediate tonic inhibition, Abnormal expression of Bcl2, Bax and PKC in nasal polyp tissues might play an important role in the occurrence and progression of nasal polyps., JNK might be an important downstream target of PKCalpha in multidrug resistance in breast cancer, Nuclear localization of phospholipase D1 mediates the activation of nuclear protein kinase C(alpha) and extracellular signal-regulated kinase signaling pathways., SERCA2-deficiency is sufficient to impede desmosome assembly and weaken intercellular adhesive strength via a PKCalpha-dependent mechanism, implicating SERCA2 as a novel regulator of PKCalpha signaling, PKC alpha mediates beta-arrestin2-dependent nephrin endocytosis in hyperglycemia., PKC-alpha and -betaI play critical roles in the epithelial-mesenchymal transdifferentiation of renal tubular epithelial cells in response to urinary proteins., The anti-invasive effects of piperine may occur through inhibition of PKCalpha and ERK phosphorylation and reduction of NF-kappaB and AP-1 activation, leading to down-regulation of MMP-9 expression., PKCalpha is the key participant in the activation of ADAM17., PKCalpha is the major contributory factor in melanoma vasculogenic mimicry., Overexpression of PRKCA is associated with non-small cell lung cancer with brain metastasis., capsaicin-mediated IL-6 increase in prostate cancer PC-3 cells is regulated at least in part by TNF-alpha secretion and signaling pathway involving Akt, ERK and PKC-alpha activat, A novel pathway of Btk regulation via protein kinase C phosphorylation of IBtkgamma., Data show that PKCalpha activation elicits a cascade of orchestrated phosphorylation events that may modulate eIF4G1 structure and control interaction with the eIF4E kinase, Mnk1., Data indicate that pure curcumin attenuates WT1 auto-regulatory function through inhibition of PKCalpha signaling in K562 cells., Dual function of protein kinase C (PKC) in TPA-induced MnSOD expression, The nuclear binding of pri-microRNA 15a is a novel function of protein kinase C alpha, which plays an important role in endothelin-1 mediated signaling., The results demonstrate that PKCalpha suppresses the expression of STC1 in breast cancer cells., PKCalpha is involved in the CCR7/NF-kappaB autocrine signaling loop in squamous cell carcinoma of head and neck., the effect of curcumin on PKCalpha activity was related to its effect on the membrane, which may modulate the binding of the enzyme to the membrane., These findings demonstrate that specific host factors involving cPLAalpha and cysteinyl LTs contribute to type III GBS penetration of the blood-brain barrier and their contribution involves PKCalpha., The authors have identified a protein kinase C (PKC) phosphorylation site within the cytoplasmic domain of the beta-subunit of the GlyR (residue S403) that causes a reduction of the binding affinity between the receptor and gephyrin., Tauroursodeoxycholate inhibits neointimal hyperplasia by reducing proliferation and inducing apoptosis of smooth muscle cells by suppression of ERK via PKCalpha-mediated MKP-1 induction., Ca(2+) influx through reverse mode NCX is required for the activation and the targeting of PKCalpha to the plasma membrane, an essential step for VEGF-induced ERK1/2 phosphorylation and downstream EC functions in angiogenesis, High levels of protein kinase C alpha expression were associated with cellular differentiation in squamous cervical cancer., PKC-mediated remodeling of the actin cytoskeleton is likely regulated by the ability of SSeCKS to control PKC signaling and activity through a direct scaffolding function, PKC alpha regulates Sendai virus-mediated interferon induction through HDAC6 and beta-catenin, Exercise induces FXYD1 phosphorylation at multiple sites in human muscle; in mice, contraction-induced changes in FXYD1 phosphorylation are fiber-type specific and dependent on protein kinase Calpha activity., Data establish the requirement of scaffolding to DLG1 for PKCalpha to promote cellular migration., VCAM-1 activation of endothelial cell NADPH oxidase/PKCalpha/PTP1B induces transient ERK1/2 activation that is necessary for VCAM-1-dependent leukocyte transendothelial migration., elevated expression of in breast cancer cells may be correlated with the potential of cell migration and invasion, expression higher in breast tumors than in the adjacent normal breast tissue, New protein synthesis and trafficking through the Golgi are required for protein kinase C alpha-induced CD36 phosphorylation and blocked thrombospondin-1 binding, suggesting that phosphorylation probably occurs intracellularly., phosphorylation by PKCalpha is critical for RalB-mediated vesicle trafficking and exocytosis., Reveal a central role for PKCalpha in cutaneous wound repair via changes in desmosomal adhesiveness., RhoGDI2 becomes rapidly phosphorylated at Ser31 in response to phorbol 12-myristate 13-acetate stimulation. Conventional type PKCalpha is responsible for this phosphorylation., SZ95 sebocytes express the conventional cPKCalpha; the novel nPKCdelta, epsilon, and eta; and the atypical aPKCzeta, The result indicated that protein kinase Calpha was involved in knee osteoarthritic progression, along with the increase of cell apoptosis., Data indicates that 2B15 requires regulated phosphorylation by both PKCalpha and Src, which is consistent with the complexity of synthesis and metabolism of its major substrate, DHT., a novel role for PKCalpha in the regulation of stress granule formation during cellular stress, Protein kinase C stimulates human B cell activating factor gene expression through reactive oxygen species-dependent c-Fos in THP-1 pro-monocytic cells., Although the findings showed elevated expression of Elk-1 and PKCalpha in 5637 cells, the regulator of PKCalpha in bladder cancer cells is yet to be determined., Protein kinase C alpha represents one of the early targets activated in response to pneumonia associated pneumolysin exposure in the lung., Results indicate a role for PKCalpha in memory and suggest a genetic link between memory and the risk for posttraumatic stress disorder (PTSD)., High levels of CCL2 expressed in bladder cancer mediates tumor invasion and is involved with advanced tumorigenesis., Over-expression and activity of endogenous PKC-alpha is closely associated with the regulation of the multidrug resistance phenotype in human colon cancer HCT15 cells., A LQT2-associated mutation can inhibit Kv11.1 ion channel activity by perturbing a consensus site for the Ser/Thr protein kinase C alpha (PKCalpha)., Data from studies using recombinant proteins suggest that isoforms of PRKA (A kinase anchor protein 7) exhibit high-affinity interactions with isoforms of PKC (primarily PKCalpha and PKCbeta used here); AKAP7 could dictate PKC localization/function., APPL1 is a novel target in endoplasmic reticulum (ER) stress-induced insulin resistance and PKCalpha is the kinase mediating ER stress-induced phosphorylation of APPL1 at Ser(430)., DGKtheta; translocation and activity is regulated by the concerted activity of EGFR and PKC., PKCalpha constitutes a crucial component of the integrin alphav-mediated pathway(s) that promote p53 relocalization and melanoma survival., AnxA6 is a new PKCalpha scaffold to promote PKCalpha-mediated EGFR inactivation., d-alpha-tocopherol and d-gamma-tocopherol have opposing regulatory functions for ICAM-1-activated PKCalpha in endothelial cells, These data indicate that EGFR and PKC are involved in mAChR-mediated activation of ERK1/2 and RSK and the subsequent proliferation of SNU-407 colon cancer cells., Protein kinase C alpha plays a significant role in the maintenance of myometrial quiescence and must decrease at the end of pregnancy allowing myometrial activation., C. neoformans activates RhoGTPases and subsequently FAK, ezrin, and PKCalpha to promote their traversal across the HBMEC monolayer, which is the critical step for cryptococcal brain infection and development of meningitis., we provide evidence that PGF2alpha induces COX-2 expression via the FP receptor and phosphorylates CREB1 by PKC, thus increasing CREB1 binding to the COX-2 promoter and the expression of COX-2 in human amnion fibroblasts., a negative feedback loop from PKCalpha that dampened PI3K activity and invasive behavior in cells with genetic hyperactivation of the PI3K pathway., Src family kinases, PI3 kinase and protein kinase C synergize to mediate Gq-dependent platelet activation, TNF-alpha up-regulates protein level and cell surface expression of the leptin receptor by stimulating its export via a PKC-dependent mechanism, Down-regulation of protein kinase C-alpha is associated with drug resistance in ovarian cancer., alpha-Tomatine inhibited 12-O-tetradecanoylphorbol-13-acetate-induced expressions of PKC-alpha in MCF-7 cells., Activation of PKC is an important step in the translocation of ANCA antigens and C5a-induced activation of neutrophils by ANCA., PKC regulates the secretion of apoE from primary human macrophages, A significant part of ROS production in sickle cells is mediated enzymatically by NADPH oxidase, which is regulated by protein kinase C, Rac GTPase, and intracellular Ca(2+) signaling within the sickle red blood cells., PKC-alpha regulates claudin-1 via Snail- and mitogen-activated protein kinase/ERK-dependent pathways during EMT in pancreatic cancer., These results suggest that serum activated PKCalpha is a reliable biomarker, applicable to lung cancer diagnosis., VEGF and PKC promote degradation-independent protein ubiquitination of FLNB to control intracellular trafficking of HDAC7., PKCalpha protein is upregulated in gastric carcinoma. PKCalpha protein expression is statistically correlated with age, histologic type, tumor differentiation, depth of invasion, angiolymphatic invasion, pathologic stage, and distant metastasis., novel and widespread mechanism of desensitization of PKCalpha signaling that involves endocytic trafficking and lysosome-mediated degradation of the mature, fully phosphorylated protein., PKC alpha plays central role in mediating HGF-induced fluctuant ERK-paxillin signaling, probably via the regulation of endosomal degradation of c-Met for the migration of HepG2., PGE2-induced activation of angiogenesis is mediated via syndecan-4-dependent activation of PKCalpha., protein kinase C alpha was upregulated in kidney carcinoma., Knockdown of protein kinase C alpha and delta enhances nanog expression in cancer cell lines., Electrostatic and hydrophobic interactions differentially tune membrane binding kinetics of the C2 domain of protein kinase Calpha., The degradation of zonula occludens-1 (ZO-1), and claudin-2 exhibited a great dependence on the activation of the transient receptor potential melastatin (TRPM) 2 channel, phospholipase Cgamma1 (PLCgamma1) and the protein kinase Calpha (PKCalpha) signaling cascade., ATPgammaS induced prostaglandin E2 generation via a cPLA2/COX-2-dependent pathway., A novel, time-dependent change in the relationship between total ERK and phosphorylated ERK levels that persists without negative feedback, is reported., This study identifies PKCalpha, PKCepsilon, and vimentin as key factors affecting efficient infection and transduction by echovirus 1 and baculovirus, respectively., These results suggest that serum activated PKCalpha is a good biomarker applicable to cancer diagnosis., Data indicate that a PKCa-independent mechanism of IL6 gene activation is very sensitive to physical forces in thyroid cells cultured in vitro as monolayers., Active PKCalpha phosphorylates Src to induce PI-3K to phosphorylate AKT that subsequently activates the ERK1/2 cascade to stimulate goblet cell proliferation., Sirolimus-FKBP12.6 impairs endothelial barrier function by activation of protein kinase C-alpha and downstream disruption of the p120-VE cadherin interaction in vascular endothelium., Data indicate that catalytically active non-structural protein 3 (NS3) NTPase/helicase can act in an analogous manner to shorter NS3 fragments as a pseudosubstrate inhibitor of protein kinase C (PKC)., phosphorylated PKCalpha is a direct target for agonist-induced proteasomal degradation via an Hsp-regulated mechanism, and highlight the existence of a novel pathway of PKC desensitization in cells., Cysteinyl leukotrienes signaling downstream of CysLT1R in mast cells is differentially regulated by two distinct PKCalpha and PKC epsilon., These results provide further support for the contribution of PKCs in Niemann Pick Type C1 disease pathogenesis., Protein kinase C alpha is a central signaling node and therapeutic target for breast cancer stem cells., miR-203 inhibits cell proliferation and migration of lung cancer cells by targeting PKCalpha., Elevation of protein kinase Calpha stimulates osteogenic differentiation of mesenchymal stem cells., results suggest that PKCalpha can modify PP2A activity by phosphorylation of B56alpha at Ser(41). This interplay between PKCalpha and PP2A represents a new mechanism to regulate important cellular functions like cellular Ca(2+) homeostasis., Differential protein kinase C-dependent modulation of Kv7.4 and Kv7.5 subunits of vascular Kv7 channels., PKCalpha/beta is critical for PLCepsilon-mediated cancer cell invasion and migration, Calcium oscillations induced by activation of the Ca2+-sensing receptor in response to an increase in extracellular or exposure to the calcimimetic R-568 result from negative feedback involving PKCalpha-mediated phosphorylation of the CaR at Thr(888)., PRKCA activity suppresses the level of ER-alpha expression by inhibiting c-JUN phosphorylation., Hydroxytyrosol, at nutritionally relevant concentrations, reduces MMP-9 and COX-2 induction in activated human monocytes via PKCalpha and PKCbeta1 inhibition, SNAIL expression was attenuated by knockdown of EGR-1, but upregulated by ectopic expression of EGR-1., The study reveals that PKC-alpha is the primary isoform mediating the activation of Nox5., Results indicated that the two PRKCI SNPs were jointly associated with prostate cancer risk in an Eastern Chinese population., Protein kinase C alpha signaling regulates netrin-1/UNC5B pathway in bladder cancer., PKCalpha first docks to the membrane via its C2 domain, and then its C1A domain embeds itself in the bilayer., PKA turnover by the REGgamma-proteasome modulates FoxO1 cellular activity and VEGF-induced angiogenesis., These findings call attention to PKC-mediated phosphorylation of alpha-tubulin as a novel mechanism for controlling the dynamics of microtubules that result in cell movement., Moreover, we have shown that phosphorylated catalytically competent PKCalpha is critical for U87 glioma cell viability in response to HypPDT treatment., By treatment of cells with octaarginine (R8), enhanced clustering of syndecan-4 on plasma membranes and binding of PKC-alpha to the cytoplasmic domain of syndecan-4 were observed., Disruption of the homodimer results in a loss of PKC-mediated ERK1/2 phosphorylation, whereas disruption of the auto-inhibited state promotes the homodimer and prolongs PKC membrane localization., Knocking down Wnt5b expression reduced phospho-PKCA levels and cell migration., PRKCA polymorphism changes the neural basis of episodic remembering in healthy individuals., Results show that Wnt5a promoted epithelial-mesenchymal transition via PKCalpha in epithelial ovarian cancer., PKC alpha is down-regulated by miR-200b in triple-negative breast cancer., The results demonstrate LPA-stimulated migration in oral carcinoma cells through LPAR3, mediated further by PKC, which acts either in concert with or independently of EGFR transactivation, T-ALL patients with PKCalpha down-regulation, compared to patients with PKCalpha levels above the threshold, presented a markedly increased cumulative incidence of relapse, results suggest that the association of PKCalpha with the armadillo repeats of beta-catenin placed the Ser33/37/Thr41 residues of beta-catenin in close proximity to PKCalpha, thereby facilitating PKCalpha-mediated beta-catenin phosphorylation, Functional variations modulating PRKCA expression and alternative splicing predispose to multiple sclerosis., Whole exome sequencing followed by immunohistochemistry of fibrolamellar hepatocellular carcinoma cell lines and tumors showed two structural variants resulting in fusion transcripts, These results are consistent with a model in which binding of OspE to PDLIM7 during infection regulates the activity of PKC isoforms that bind to the PDLIM7 LIM domain., The PKC/GSK-3beta signaling pathway controls both the stability and transcription of Snail, which is crucial for epithelial-mesenchymal transition induced by EGF in PC-3 and A549 cells., CD44/selectin binding signals increased intercellular adhesion molecule 1 up-regulation on the endothelial cells (ECs)surface through a PKCalpha-p38-SP-1 pathway, which further enhances melanoma cell adhesion to ECs during metastasis, Activation of PKC-alpha and -delta mediates a novel positive feedback loop by promoting ErbB2 entry into the endocytic recycling compartment., Data suggest that calcium-dependent phosphatidylinositol 4,5-diphosphate- (PI(4,5)P2-) binding proteins (such as PRKCA, SYT1 [synaptotagmin I], and ANXA2 [annexin A2]) interactions with membrane microdomains are tightly regulated. [REVIEW], INPP4B is a novel suppressor of oncogenic PKC signaling, further emphasizing the role of INPP4B in maintaining normal physiology of the prostate epithelium and suppressing metastatic potential of prostate tumors., KLHL3 is phosphorylated at serine 433 in the Kelch domain (a site frequently mutated in hypertension with hyperkalemia) by protein kinase C in cultured cells and that this phosphorylation prevents WNK4 binding and degradation., PKCa and Cyclin B1 are linked in a DAG-dependent mechanism that regulates cell cycle progression, contributes to high NaCl-dependent activation of NFAT5 through ERK1/2, the synapse-associated protein-97 (SAP97), an excitatory synapse scaffolding element, governs ADAM10 trafficking from dendritic Golgi outposts to synaptic membranes, mediated by a previously uncharacterized protein kinase C., The suppression of PKC activates the Chk1-mediated mitotic exit checkpoint in Nf1-deficient cells, leading to the induction of apoptosis via mitotic catastrophe., These results show a key participation of PKCalpha and PKCdelta in progesterone receptor regulation and function., The expression of protein kinase Calpha may be regulated by miRNA-328, which in turn may promote brain metastasis from lung cancer., Endogenous NLGN4X is intensely phosphorylated on T707 upon PKC stimulation in human neurons., Data indicate that rotein kinase calpha (PKCalpha) plays a role in downregulating complement receptor Ig (CRIg coded by V-set and Ig domain-containing protein 4 VSIG4) expression., Data indicate that cellular glucose deprivation activates protein kinase C alpha-(PKCalpha) to induce both autophagy and degradation of beta-catenin., Data show that in K562 cells, the protein kinase C alpha (PKCalpha) and protein kinase C beta II (PKCbetaII) expressions enhanced in the presence of the drug when the growth was inhibited., Whereas ectopic overexpression of PKCalpha in parental H1650 cells was not sufficient to alter the expression of EMT genes., Data indicate a direct correlation between the protein kinase C alpha (PKC-alpha) and ribonuclease III Dicer., Our data also suggest that PKCalpha is important for both mesenchymal and amoeboid invasiveness, making it an attractive target for anti-metastatic therapies, We present the current knowledge of protein kinase C (PKC)-dependent regulation of Cx43 and discuss the divergent results., Taken together, our present study demonstrated that PKC regulates the function of OATP1B1 by affecting internalization and recycling of the transporter protein., These findings suggest that PKCalpha expression in HCC could be stimulated by the formation of MZF-1/Elk-1 complex, which directly binds to the PKCalpha promoter., results indicate that PKC-mediated cortactin phosphorylation might be implicated in the maintenance of growth cone, Aurora kinases ((Aurora kinase A and B )mediate PKC-MAPK signal to NF-kappaB/AP-1 with increasing MMP-9 expression and invasion of MCF-7 cells., findings demonstrate that PKCalpha plays a critical role in HCC development by inducing DUOX2 expression and ROS generation, and propose a strategy to target PKCalpha/DUOX2 as a potential adjuvant therapy for HCC treatment, These results suggest that over-activated ERK and PKC pathways are involved in the P2Y2R-mediated invasion of breast cancer cells., this study identified PKC as the kinase that phosphorylates a specific site in the linker region of PACSIN2., Syndecan-4 is essential for transmitting the mechanotransduction signals via activation of PKC-alpha and is important for tumor cells spreading, assembly of actin cytoskeleton and cell contractility., we suggest that PKCA tightly controls TRM6/61 activity to prevent translation deregulation that would favor neoplastic development., These data establish a role for FMNL2 in the regulation of beta1-integrin and provide a mechanistic understanding of the function of FMNL2 in cancer invasiveness., Our data suggest that PKCalpha, beta and epsilon activation may underlie physiological and pathophysiological responses of alpha1-AR signaling for the phosphorylation of membrane-associated substrates including ion-channel and transporter proteins., The results suggest that PKC-delta is an essential part of the apoptotic program in mesothelioma cells, whereas PKC-alpha mediates a pro-survival response to cisplatin., lipids mediate post-transcriptional regulation of HAMP through PKC- and HuR-dependent mechanisms, InB may exhibit growth-inhibitory activity through the activation of PKCalpha, followed by an increase in NFAT transactivation ability., PKCalpha is coupled to ATP-stimulated TMEM16A activation in biliary epithelial cells., Data show that bisindolylmaleimides (BIMs) Ro 31-8220 also blocks activity of the solute carrier organic cation transporter 1 (OCT1), involved in uptake of marketed drugs in the liver, in a protein kinase C (PKC)-independent manner., This study showed that SLC44A1-PRKCA fusion seems to be a specific characteristic of Papillary glioneuronal tumors with a high diagnostic value., RNA sequencing identified a novel ATPase, Ca2+ transporting, plasma membrane 4(ATP2B4)-protein kinase C-alpha (PRKCA) fusion transcript., Prolonged membrane association/activation of PKCalpha is seen in self-renewing epithelium of the intestine, cervix, and skin., High P-PKCalpha expression in neoplastic gastric cancer biopsy samples as compared to nonneoplastic samples suggests that P-PKCalpha might act as an indicator of gastric cancer progression.,
OMIM_DISEASE Pituitary tumor, invasive,
SP_COMMENT catalytic activity:ATP + a protein = ADP + a phosphoprotein., cofactor:Binds 3 calcium ions per subunit. The ions are bound to the C2 domain., function:PKC is activated by diacylglycerol which in turn phosphorylates a range of cellular proteins. PKC also serves as the receptor for phorbol esters, a class of tumor promoters., function:This is a calcium-activated, phospholipid-dependent, serine- and threonine-specific enzyme. May play a role in cell motility by phosphorylating CSPG4., similarity:Belongs to the protein kinase superfamily., similarity:Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily., similarity:Contains 1 AGC-kinase C-terminal domain., similarity:Contains 1 C2 domain., similarity:Contains 1 protein kinase domain., similarity:Contains 2 phorbol-ester/DAG-type zinc fingers., subunit:Interacts with ADAP1/CENTA1, CSPG4 and PRKCABP. Binds to SDPR in the presence of phosphatidylserine.,
protein kinase C beta(PRKCB) protein kinase C beta(PRKCB) Related Genes Homo sapiens
CHROMOSOME 16,
CYTOBAND 16p11.2,
ENSEMBL_GENE_ID ENSG00000166501,
GENERIF_SUMMARY Investigation of the inhibitory effects of chelerythrine chloride on the translocation of the protein kinase C betaI, betaII, zeta in human neutrophils, PKC-beta 1 when activated enhances calcium flux and protects the assembly of the F-actin cytoskeleton in intestinal monolayers against oxidants., A method that uses liquid chromatography electrospray ionization-mass spectrometry to quantify site-specific protein phosphorylation was used to measure the time-dependent increase of phosphorylation by PRKCB2 at a PKC-preferred site, Ser44., PKC beta II expressed in human neutrophils can phosphorylate p47phox and induce both its translocation and NADPH oxidase activation as well as the binding of p47phox to the cytosolic fragment of p22phox., The turn motif is a phosphorylation switch that regulates binding of Hsp70., REVIEW, Nephroprotective actions of the ACE inhibitor lisinopril in experimental diabetes mellitus were associated with and thus could be mediated in part by inhibition of diabetes-induced activation of PKC beta isoenzymes in the renal cortex., PKCbeta has a role in in the chemotactic response of human monocytes to MCP-1, elevated glucose increases the activity of core 2 GlcNAc-T and adhesion of human leukocytes to retinal capillary endothelial cells, in a dose-dependent manner, through diabetes-activated serine/threonine protein kinase C beta2 dependent phosphorylation, DNA sequence differences in the promoter of PRKCB1 contribute to diabetic nephropathy susceptibility in type I diabetes mellitus, data indicate a highly specific function of PKCbeta for regulation of TCR-CD28 induced-signaling, IL-2 gene expression and secretion in Jurkat T cells, PKCalpha and betaII have roles in the regulation of membrane recycling, protein kinase Cbeta is a direct, downstream target of RUNX1, EGF-mediated protection against oxidant disruption of the intestinal barrier function requires PKC-beta1 activation and NF-kappaB suppression., These results suggest that phosphorylation of tyrosinase by PKC-beta induces a complex formation between tyrosinase and TRP-1., PKCbetaII induces cell invasion through a Ras/Mek-, PKC iota/Rac 1-dependent signaling pathway, phospholipase D causes translocation of protein kinase C (PKC)betaII but not PKCbetaI to a juxtanuclear subset of recycling endosomes, RACK-I anchors activated PKC-beta on the melanosome membrane, allowing PKC-beta to phosphorylate tyrosinase, Protein kinase CbetaII regulates its own expression in rat intestinal epithelial cells and the colonic epithelium in vivo., PKC-MAPK pathway mRNAs plays an important role in the development and/or progression of early tissue damage in diabetic nephropathy, results showed that PKC beta(II) and delta isozymes are essential for the activation of IL-10 production in human monocytes following stimulation by HIV-1 Tat protein, We analyzed the dependence of the expression of some selected protein kinase C isoenzymes on the availability and/or action of androgens., juxtanuclear translocation of protein kinase C betaII is selectively inhibited by a negative feedback mechanism involving ceramide formed from the salvage pathway, Chemotaxis to PDGF-BB in 25 mmol/L glucose is PKCbetaII-dependent and requires activation of both the PI3K and MAPK pathways., PKCbetaII is regulated by PI 3-kinase in HT29 cells, the level of Smad6s can alter the level of TGF-beta and the subsequent induction of PAI-1 via a FoxD1 transcription site, This evidence supports that the Hal gene is turned on by glucocorticoids and by glucagon either via PKC or PKA, but prefers the PKA pathway., Inhibition of protein phosphatase 2A increased phosphorylation at Ser660 that determines calcium sensitivity and activity of protein kinase c betaII isoform, Regulation of protein kinase C betaII expression and signaling play critical roles in mediating progenitor to dendritic cell differentiation, PRKCB1 gene on chromosome 16p may be involved in the etiology of autism., The data do not support a strong association between single nucleotide polymorphism of PRKCB and spina bifida risk., Furthermore, curcumin strongly repressed the PMA-induced phosphorylation of ERK, JNK, and p38 MAP kinase, which were dependent on the PKC pathway, Acrosomal exocytosis is regulated through the PKC-mediated phosphorylation of conserved threonines in the polybasic regions of synaptotagmin VI., Data show that activity of protein kinase B in hormone-dependent mammary tumors was significantly higher than in tumor tissue from patients with negative receptor status., A novel mechanism by which ROS can initiate cell death through the activation of PKC-betaI is reported., Protein kinase C can inactivate TRPC3 indirectly by activating protein kinase G, and directly by phosphorylation on Ser-712., Protein kinase Calpha, betaI, and betaII isozymes regulate cytokine production in mast cells through MEKK2/ERK5-dependent and -independent pathways., Subcellular localization of protein kinase C (PKC)-beta, CD81, and LFA-1 was determined in T lymphocytes., increased expression of PKC-alpha and -betaI leads to increased total classical PKC kinase activity; increased activity of the isoenzymes plays a role in accelerated growth of TCC. In carcinoma tissue, PKC expression and activity are under strict control., study indicates that PRKCB1 is a predictor for worsening of kidney disease in Japanese subjects with type 2 diabetes, Thus PKC-beta2 is hypothesized to participate in the regulation of CFTR apical plasma membrane targeting within the constitutive cellular biosynthetic pathway., PKC-beta-dependent augmentation of transcellular ISC-cAMP at the level of the basolateral membrane demonstrated that transport events with geographically distinct subcellular membranes can be independently regulated by the PKC beta-isoform., These results indicate that Hcy (homocysteine)-stimulated superoxide anion production in monocytes is regulated through PKC-dependent phosphorylation of p47phox and p67phox subunits of NADPH oxidase., effect of insulin is dependent on activation of PKCalpha and/or PKCbeta, and these insulin signals may interfere with the dynamic assembly/disassembly and/or distribution of F-actin, which is required for the phagocytosis process, Incubation of podocytes with membranous glomerulonephritis sera determined strong upregulation of pPKC-alpha/beta that was reverted by pre-incubation with clusterin, Data describe the role of angiotensin II type 1A receptor phosphorylation, phospholipase D, and extracellular calcium in isoform-specific protein kinase C membrane translocation responses., The suppressive effects on MDR3 mRNA of PMA were attenuated in antisense PKCbeta-treated cells. PKCbeta plays a regulatory role in the expression of MDR3., beta and some other PKC isoenzyme, most likely delta, mediate cholesterol accumulation when macropinocytosis of LDL is stimulated in PMA-activated human monocyte-derived macrophages, overexpressed active PKCbetaII plays a role in the regulation and outcome of BCR signals that can be important for the progression of CLL, structure of the Rac1-PLC-beta2 complex reveals determinants that dictate selectivity of PLC-beta isozymes for Rac GTPases over other Rho-family GTPases, Findings indicate that IL-1beta-induced Cox-2 expression in human myometrial smooth muscle cells is dependent on the action of atypical PKCs, through stimulation of the activity of NF-kappaB., Data do not support the finding that the PRKCB1 gene variants contribute risk for the development of autism., hBVR activation of PKC betaII underscores its potential function in propagation of signals relayed through PKCs, the cell fate commitment of CD14(+)monocytes towards MDMs or MoDCs appears to be steered by the selective activation of PKCalpha or PKCbeta(I), respectively., PTH induces an increased activity of the eNOS system through PKA and PKC pathways, HGF signaling process from Gab1 to PI3K is negatively regulated by PKC-betaII, and its loss is critical for melanoma cells to gain invasive potential., the compartmentalization of HLA-DR/CD18 complex within or outside lipid rafts as a mechanism through which HLA-DR can integrate both PTK and PKCbeta signals leading to activation and death, Differential protein kinase C isoform abundance was observed in thoracic aortic aneurysm samples from patients with bicupsid valve versus those with tricupsid valve, suggesting independent molecular signaling pathways may be operative., PKC-beta I and II are differently distributed in the two prognostic subgroups of de novo diffuse large B-cell lymphoma., Data show that expression of DMPK-CUG-repeat RNA results in hyperphosphorylation and stabilization of CUGBP1, and suggest that inappropriate activation of the PKC pathway contributes to the pathogenic effects of a noncoding RNA., the -546 polymorphism in the PKCbeta promoter reduces promoter activity, which leads to a decreased expression of PKCbeta2 and subsequently is associated with decreased peripheral insulin-dependent glucose uptake, PLCgamma-mediated activation of PKCepsilon and PKCbetaI and intracellular calcium is involved in EGF-mediated protection of tight junctions from acetaldehyde-induced insult, Data suggest that foreign body giant cell formation is supported by PKCbeta, PKCdelta, and PKCzeta in combined diacylglycerol-dependent (PKCbeta and PKCdelta) and -independent (PKCzeta) signaling pathways., discrete PKCs trigger distinctive responses when activated in different phases of the cell cycle via a common mechanism that involves p21 Cip1 up-regulation., The phosphorylation of ERK(1/2) and p38 MAPK was regulated by upregulated protein kinase C beta (PKC beta) in hepatocellular carcinoma., Cx43Hc electrical conductance is inhibited after PKC activation. Inhibition is predominantly mediated by PKC-epsilon. Partial inhibition may be provided by PKC-beta II/PKC-delta., PKC-beta is upregulated at the gene expression level in human diabetic nephropathy., Probiotic-secretory proteins protect the intestinal epithelium from hydrogen peroxide-induced insult by a PKC beta1/epsilon- and ERK1/2-dependent mechanism., the E3 activity of RBCK1 is controlled by two distinct manners, interaction with RBCK2 and phosphorylation by PKCbeta, The results of this study confirmed the existence of a significant association between PRKCB1 gene variants and autism., These findings demonstrate a central role for PKC-beta, and particularly PKC-betaII in the development of tubulointerstitial fibrosis., PKC delta in preeclamptic placentas promotes Bax dissociation from 14-3-3 zeta through 14-3-3 zeta phosphorylation., PRKCB2 (protein kinase C beta2) and PKCdelta (protein kinase C delta) counter-regulate coronary endothelial barrier properties by targeting distinctive subcellular sites., Taken together the results of the present study show that PKCbetaII can act as a specific PKC isoform regulating translation, in an mTOR-independent fashion, possibly close to the ribosomal machinery., The expression of P-cadherin (a marker of proliferating keratinocytes) was regulated by all of the examined protein kinase C isoenzymes, also in an antagonistic manner (inhibited by cPKCalpha/nPKCdelta and stimulated by cPKCbeta/nPKCepsilon)., Upregulation of PKCbetaII is associated with increased angiogenesis and prostate tumor cell proliferation, protein kinase C betaII augments NF-kappaB-mediated TNF-alpha-induced transcription of the target gene CCL11, promoting p65 association with the CCL11 promoter, in human airway smooth muscle cells by phosphorylating p300/CBP-associated factor, These data show that native ribosomes host active PKC and hence allow the phosphorylation of ribosome-associated substrates like initiation factors and mRNA binding proteins., Nonspecific inhibition of PKCbeta prevents LDL uptake in macrophages. These findings suggest that PKCbeta inhibitors may represent a novel class of antiatherosclerotic drugs., C-terminal tail and determinants in the alphaE-helix of the catalytic domain allows the chaperones Hsp90 and Cdc37 to bind newly synthesized PKC beta II, a required event in the processing of PKC by phosphorylation, PKCbeta plays a key role of in HCC motility and PKCbeta may be a potential therapeutic target., PRKCB was necessary for in vitro survival of chronic lymphocytic leukemia cell lines., The immunohistochemical detection of PKC-beta II in patients with colorectal cancer is described., PKCbeta(2) plays a major role in TNF-alpha-induced human vascular endothelial cell apoptosis., Report expression of protein kinase A and C subunits in post-mortem prefrontal cortex from persons with major depression and normal controls., YadA and invasin of Yersinia pseudotuberculosis both trigger signal transduction pathways during integrin-mediated phagocytosis into epithelial cells, which lead to the activation of Akt, PLC-gamma1, PKCalpha and -beta downstream of PI3 kinase., These results suggest that swiprosin-1 is a PKC-beta I/eta-inducible gene and it modulates mast cell activation through NF-kappaB-dependent pathway., Protein kinase Cbeta modulates ligand-induced cell surface death receptor accumulation, PMA-responsive cPKC isoforms (alpha, beta and gamma) play a key role in negative regulation of CD98 signalling and homotypic aggregation, Recruitment of PKC-betaII to lipid rafts mediates apoptosis-resistance in chronic lymphocytic leukemia expressing ZAP-70., down-regulated expression of PKCbetaII is associated with HBV infection in human hepatocellular carcinoma, Results indicate that a depletion of the WRN protein in normal fibroblasts causes the activation of several PKCs through translocation and association of RACK1 with such kinases., The PKCbetaII was localized to the mitochondria, and inhibition of PKCbeta significantly reduced UV-induced reactive oxygen species in neoplastic melanocytes with high PKCbetaII expression., Study suggests the necessity for assessing the subcellular localization of PKCbetaII in breast cancer subtypes when evaluating the possible effectiveness of PKCbetaII-targeting agents., Our results suggest lack of association of PRKCB1 gene promoter polymorphisms and moderate protective association of PEDF gene polymorphism with diabetic retinopathy in the south Indian population., VEGF, in addition to its role in providing prosurvival signals, also plays a role in overexpression of PKCbetaII, an enzyme with a specific pathophysiologic role in chronic lymphocytic leukemia, TRPC3 functions as both a Ca(2+)-permeable channel and a protein scaffold at the plasma membrane for downstream PKCbeta activation in B cells., phosphorylation of histone H3 at threonine 6 (H3T6) by protein kinase C beta I (PKCbeta(I), also known as PRKCbeta) is the key event that prevents LSD1 from demethylating H3K4 during AR-dependent gene activation, the single amino acid substitution identified in lung cancer cell lines did not affect enzastaurin's antiproliferative or phosphorylation-inhibitory activity, In conclusion, PKC activation, opening of mitoK(ATP) channels and p38 MAPK activation in early reoxygenation induced the postconditioning of human myocardium, in vitro., Data propose that PKC suppresses store-operated Ca(2+) entry and Ca(2+) release-activated Ca(2+) (CRAC) channel function by phosphorylation of Orai1 at N-terminal serine residues Ser-27 and Ser-30., intracellular Francisella tularensis novicida triggers temporal and early activation of Ras through the SOS2/GrB2/PKCalpha/PKCbetaI quaternary complex; Ras signalling by intracellular F. tularensis is essential for intracellular proliferation in the cytosol, Genetic variants in the PRKCB1 gene were independently associated with development of ESRD in Chinese patients with type 2 diabetes., requirement for PKCbeta in IL-2 secretion/transcription and IL-2R regulation., Two novel susceptibility loci, PRKCB and 8p11.21, have been identified for systemic lupus erythematosus., PKC-alpha and -betaI play critical roles in the epithelial-mesenchymal transdifferentiation of renal tubular epithelial cells in response to urinary proteins., APE1 suppresses oxLDL-induced p66shc activation in endothelial cells by inhibiting PKCbetaII-mediated serine phosphorylation of p66shc, and mitigates vasoconstriction induced by activation of PKC., Results establish a causative role for PKCbetaII and L-plastin in linking GM-CSF-induced eosinophil priming for chemotaxis., oxidized LDL also increased phosphorylation of protein kinase C beta(2) (PKCbeta(2)) at both Thr641 and Ser660, as well as c-Jun N-terminal kinase, PKCbeta plays an important role in Acquired immunodeficiency syndrome (AIDS)-related non-Hodgkin lymphoma survival., activation of phospholipase C and protein kinase C-beta 2 by the IGF-II/mannose-6-phosphate receptor are required for the activation of sphingosine kinase 1., C-peptide increases Na,K-ATPase expression via PKC- and MAP kinase-dependent activation of transcription factor ZEB in human renal tubular cells, These data show that the impact of PKC on G(q) signal transduction is determined by the background of cell-specific processes., PRKCB may be a potential predictor of calcineurin inhibitor (CNI)-induced nephrotoxicity in heart transplant recipients, and could therefore be a promising candidate to identify patients who are most susceptible to this adverse drug reaction., Data indicate PKCbetaII as a novel inhibitor of proteasomal function., PKC signaling modulates osteoblast differentiation, at least in part, through the regulation of Msx2., Data from studies using recombinant proteins suggest that isoforms of PRKA (A kinase anchor protein 7) exhibit high-affinity interactions with isoforms of PKC (primarily PKCalpha and PKCbeta used here); AKAP7 could dictate PKC localization/function., Comp of gene expression between PROX1-overexpressing and mock-transfected cells revealed that the expression of PRKCB2 is down-regulated in PROX1-overexpressing cells. A PRKCB inhibitor suppressed growth of control cells more than PROX1-expressing cells., We found that transcriptional activation of PRKCB was directly regulated by the chimeric fusion oncogene EWSR1-FLI1 that drives ewing sarcoma growth., Estrogen receptor-alpha, RBCK1, and protein kinase C beta 1 cooperate to regulate estrogen receptor-alpha gene expression., Our findings implicate PKCbeta activity in endothelial insulin resistance., Inhibition of PKCbeta enhanced apoptosis of human autoreactive B cells., The expression of protein kinase C (PKC)-betaII and the subsequent activation of NF-kappaB in bone marrow stromal cells are prerequisites to support the survival of malignant B cells., Genetic variation in protein kinase C type beta may contribute toward the interindividual variation in DHV constriction responses to alpha2-AR activation by the agonist dexmedetomidine, PKCalpha and PKCbeta cooperate in IL-2 transcriptional transactivation in primary mouse T cells independently of the actions of PKCtheta;., Protein kinase Cbeta critically regulates dopamine D2 autoreceptor-activated dopamine transporter trafficking., HIF1alpha and PKCbeta have roles in mediating the effect of oxygen and glucose during wound healing, Data suggest that hyperglycemia promotes cerebral-barrier dysfunction through activation of PKCbeta and consequent stimulation of oxidative stress and tight junction dissolution., established an important role for PKCbeta1 in PANC1 cells suggesting it would act as a suppressor of tumorigenic behavior in pancreatic cancer, The translocation of PKCBetaII was induced by soluble amyloid Beta precursor protein alpha., PKCbeta is the isoform responsible for Syk negative regulation, Normalization of glucose levels and silencing PKCB activity neutralized the effects of hyperglycemia on occludin and RhoA/Rho-kinase/MLC2 expression, localization, and activity and consequently improved in vitro blood-brain barrier integrity and function., Vimentin is a phosphorylation target of PKC-beta in MCP-1-treated monocytes and that PKC-beta phosphorylation is essential for vimentin secretion., These results provide further support for the contribution of PKCs in Niemann Pick Type C1 disease pathogenesis., CD40L may contribute to atherogenesis via PRKCB by activating endothelial cells and recruiting monocytes to them., PKCalpha/beta is critical for PLCepsilon-mediated cancer cell invasion and migration, Protein kinase C beta is important for the regulation of NHE-1 activity, which is associated with ERK1/2-p90RSK signaling pathways as a kinase of NHE-1 in cortical neuronal cells exposed to glutamate., Hydroxytyrosol, at nutritionally relevant concentrations, reduces MMP-9 and COX-2 induction in activated human monocytes via PKCalpha and PKCbeta1 inhibition, shRNA knockdown of PKCbeta reduced cellular proliferation, colony formation, and migratory capacity of melanoma cells and also reduced lung colonization of stably transduced melanoma cells in mice., This review summarizes the current knowledge of both PKCbeta and PKCdelta isoforms during atherogenesis, and addresses differential roles and disputable observations of PKC isoforms., STAT3 bound to previously undescribed negative regulatory elements within the promoter of PRKCB, which encodes PKCbetaII., PRKCB2 is specifically required for mTORC2-dependent AC9 activation and back retraction during neutrophil chemotaxis., isoform betaII plays a central role in the PKC-dependent regulation of Kv1.5/Kvbeta1.2 channels., The detected PDPN-PRKCB, CD63-PRKCD and LAMTOR1-PRKCD gene fusions are all predicted to result in chimeric proteins consisting of the membrane-binding part of PDPN, CD63 or LAMTOR1, PKCbeta2 inhibition protects mice from gut ischemia-reperfusion injury by suppressing the adaptor p66(Shc)-mediated oxidative stress and subsequent apoptosis., Pharmacological inhibition PRKCB1 via their specific inhibitors and neutralisation of O2 (*-) by a cell-permeable superoxide dismutase mimetic., PMA primed PBTLs for polarization under flow, with protein kinase C (PKC)-delta enriched in the leading edge, PKC-betaI in the microtubule organizing center, and PKC-betaII in the uropod and peripheral region., Data show that in K562 cells, the protein kinase C alpha (PKCalpha) and protein kinase C beta II (PKCbetaII) expressions enhanced in the presence of the drug when the growth was inhibited., Hyperoxia can increase the expression of PKCbeta in alveolar epithelial cells and production of mitochondrial reactive oxygen species and decrease mitochondrial membrane potential., Direct interaction between the two proteins leads to Apoptin-induced activation of PKC and consequently activated PKCbetaI mediates phosphorylation of Apoptin to promote its tumour-specific nuclear translocation and cytotoxic function., Ionizing radiation-induced eNOS activation in human vascular endothelial cells is attributed to both the up-regulation of PKC-betaII and the increase in ROS generation which were independent of each other., human AKAP79-anchored PKC selectively phosphorylates the Robo3.1 receptor subtype on serine 1330, that the high-concentration glucose-induced disruption of endothelial adherens junctions is mediated by tyrosine phosphorylation of vascular endothelial cadherin through PKC-beta and myosin light chain phosphorylation, Our data indicate a new direction for LOX-1 regulation by the modulation of the PKCbeta/NAPDH oxidase/SIRT1/HSF1 mechanism, Effect of PKC-beta Signaling Pathway on Expression of MCP-1 and VCAM-1 in Different Cell Models in Response to Advanced Glycation End Products, Gene fusions involving PRKC genes occur in several morphological and clinical subsets of benign fibrous histiocytoma, but they seem to account for only a minority of the cases., Study found a significant decrease of PRCKB1 mRNA expression in subsyndromal symptomatic depression, suggesting PRKCB1 might be a candidate gene and biomarker, Lower hydrogen sulfide is associated with cardiovascular mortality, which involves PKCBII/Akt pathway in chronic hemodialysis patients., PPAR-delta and NKIRAS1 are downstream mediators in the PRKCB pathway in human umbilical vein endothelial cells., PKCbetaII inhibits the ubiquitination of beta-arrestin2 in an autophosphorylation-dependent manner,
SP_COMMENT catalytic activity:ATP + a protein = ADP + a phosphoprotein., cofactor:Binds 3 calcium ions per subunit. The ions are bound to the C2 domain., function:This is a calcium-activated, phospholipid-dependent, serine- and threonine-specific enzyme. PKC is activated by diacylglycerol which in turn phosphorylates a range of cellular proteins. PKC also serves as the receptor for phorbol esters, a class of tumor promoters. May be considered as a novel component of the NF-kappa-B signaling axis responsible for the survival and activation of B-cells after BCR cross-linking., PTM:Phosphorylation on Thr-500 of isoform beta-I, within the activation loop, renders it competent to autophosphorylate. Subsequent autophosphorylation of Thr-642 maintains catalytic competence, and autophosphorylation on Ser-661 appears to release the kinase into the cytosol. Similarly, isoform beta-II is autophosphorylated on 'Thr-640' and 'Ser-659', subsequent to phosphorylation on Thr-500. Autophosphorylated on other sites i.e. in the N-terminal and hinge regions have no effect on PKC activity., similarity:Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily., similarity:Contains 1 AGC-kinase C-terminal domain., similarity:Contains 1 C2 domain., similarity:Contains 1 protein kinase domain., similarity:Contains 2 phorbol-ester/DAG-type zinc fingers., subunit:Interacts with PDK1 (By similarity). Interacts in vitro with PRKCBP1.,
protein kinase C gamma(PRKCG) protein kinase C gamma(PRKCG) Related Genes Homo sapiens
CHROMOSOME 19,
CYTOBAND 19q13.4,
ENSEMBL_GENE_ID ENSG00000126583,
GENERIF_SUMMARY REVIEW, Missense mutations occur in the regulatory domain of PKC gamma, the affinity of isolated C1A and C1B domains of PKCalpha and PKCgamma for soluble and membrane-incorporated DAG and phorbol ester were measured by isothermal calorimetry and surface plasmon resonance in order to compare activation mechanisms, activation of mGluR5 causes translocation of both gammaPKC and deltaPKC to the plasma membrane. deltaPKC, but not gammaPKC, phosphorylates mGluR5 Thr(840), leading to the blockade of both Ca2+ oscillations and gammaPKC cycling., Spinocerebellar ataxia(SCA) type 14 is caused by mutations in PRKCG gene. The observation that all 4 PRKCG mutations identified in patients with SCA to date are located in exon 4 suggests a critical role for this region of the gene in cerebellar function., We sequenced exons 4 and 5 of PRKCG and detected a missense mutation in exon 4, involving a G-->A transition in nucleotide 353 and resulting in a glycine-to-aspartic acid substitution at residue 118 in a Dutch autosomal dominant cerebellar ataxia family, osmotic shock in human keratinocytes leads to activation of phospholipase C-gamma1, A novel missense mutation, F643L, which maps to a highly conserved amino acid of the catalytic domain of protein kinase C gamma, extends the phenotype associated with the spinocerebellar ataxia type 14 (SCA14) locus., spinocerebellar ataxia type 14 mutations make gammaPKC form cytoplasmic aggregates, which may play a role in development of SCA14, Six mutations were found that segregated with the disease including F643L (exon 18), Five new missense mutations were identified in exons 4 (C114Y/G123R/G123E), 10 (G360S) and 18 (V692G)., These results indicate that PKCgamma regulates NMHC-IIB phosphorylation and cellular localization in response to EGF stimulation., These results suggest that the PKC gamma R659S mutation is susceptible to neuronal death and is involved in the pathogenesis of neurodegenerative diseases, including Retinitis pigmentosa., The present findings show that the interaction between PKCgamma and GluR4 is specifically required to assure PKC-driven phosphorylation and surface membrane expression of GluR4., PRKCG mutation (SCA-14) causing a Ramsay Hunt phenotype., detection of a new mutation in PRKCG responsible for spinocerebellar ataxia type 14, which may be located in a mutational hot spot, Codon 101 of PRKCG, a preferential mutation site in SCA14., This study present a benign SCA14 phenotype in a German patient associated with a missense mutation in exon 3 of the PRKCG gene, PKCgamma, but not C1 domain mutants, inhibits Ca2+ influx in response to muscarinic receptor stimulation., These studies suggest that Purkinje cell damage in SCA14 may result from a reduction of PKCgamma activity due its aberrant sequestration in the early endosome compartment., The impact of three C1B regulatory subdomain mutations on the intracellular kinetics, protein conformation and kinase activity of PKCgamma in living cells, was investigated., Rac regulates the interaction of fascin with active PKC., study investigated whether mutant gammaPKC formed aggregates and how mutant gammaPKC affects the morphology and survival of cerebellar Purkinje cells (PCs), which are degenerated in SCA14 patients, ezrin is regulated during osteosarcoma metastasis by PKC, Using shotgun mass spectrometry, we found this protein differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia., Protein kinase C gamma, a causative for spinocerebellar ataxia, negatively regulates nuclear import of aprataxin., PMA-responsive cPKC isoforms (alpha, beta and gamma) play a key role in negative regulation of CD98 signalling and homotypic aggregation, The presence of unphosphorylated PKC-gamma in HT29 cells, and its complete absence in Caco2 cells demonstrates a cell type-dependent differential coupling of Thr514-phosphorylation with de novo synthesis of PKC-gamma in colon cancer cells., data support the idea that RanBP9 and RanBP10 may function as signaling integrators and dictate the efficient regulation of D(1) receptor signaling by PKCdelta and PKCgamma, These results indicate that autophagy contributes to the degradation of mutant gammaPKC, suggesting that autophagic inducers could provide therapeutic potential for SCA14., This protein has been found differentially expressed in thalami from patients with schizophrenia., Protein Kinase C gamma rs3745406 polymorphism is not significantly associated with major depressive disorder., Data show that through HINT1, the MOR facilitates the cross-talk of two NO- and zinc-regulated signal-transduction pathways, PKC/Src and Raf-1/ERK1/2, implicated in the negative control of morphine effects., SCA14, a novel mutation in the PRKCG gene, was found in two families in Norway with autosomal dominant cerebellar ataxia., cPLA(2)-dependent AA release is required for VEGF-induced Src-PLD1-PKCgamma-mediated pathological retinal angiogenesis, The Spinocerebellar ataxia type 14 is caused by mutations in the protein kinase C gamma (PKCgamma, PRKCG) gene with a hotspot for mutations in exon 4. Genetic testing for SCA14 is clinically available., We propose that variety of mutant gammaPKC characters integrally and complicatedly participate in the pathophysiology of SCA 14., Exome sequencing of large, 5-generational British kindred finds a novel p.Arg26Gly mutation in the PRKCG gene causing familial spinocerebellar ataxia 14., Spinocerebellar ataxia type 14 mutant PKC-gamma upregulates Hsp70. Hsp70 has a role in degrading mutant PKC-gamma., PKCgamma plays a critical role in cancer cells, and simultaneous inhibition of PKCgamma and Hsp90alpha synergistically prevents cell migration and promotes apoptosis in cancer cells., we show that the mutation V138E of the protein kinase C gamma (PKCgamma) C1B domain, which is implicated in spinocerebellar ataxia type 14, exhibits a partially unfolded C-terminus, findings provide evidence for both an increased PKCgamma activity in Purkinje cells in vivo and for pathological changes typical for cerebellar disease thus linking increased and dysregulated activity of PKCgamma to development of cerebellar disease, PKCgamma,mutated in the neurodegenerative disease spinocerebellar ataxia type 14 is a novel amyloidogenic protein., The rs454006 polymorphism of the PRKCG gene correlated to osteosarcoma susceptibility and might increase the risk of osteosarcoma., The results showed that carrier of rs454006*C allele and rs3745406*C might elevate the risk of osteosarcoma, Data suggest that PRKCG (protein kinase C gamma) phosphorylates TA isoforms of p63 (tumor protein p63) at Thr157 to stabilize them and promote cell apoptosis in tumor cells.,
OMIM_DISEASE Spinocerebellar ataxia 14,
SP_COMMENT catalytic activity:ATP + a protein = ADP + a phosphoprotein., cofactor:Binds 3 calcium ions per subunit. The ions are bound to the C2 domain., disease:Defects in PRKCG are the cause of spinocerebellar ataxia type 14 (SCA14) [MIM:605361]. Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA14 is an autosomal dominant cerebellar ataxia (ADCA)., function:PKC is activated by diacylglycerol which in turn phosphorylates a range of cellular proteins. PKC also serves as the receptor for phorbol esters, a class of tumor promoters., function:This is a calcium-activated, phospholipid-dependent, serine- and threonine-specific enzyme., online information:Retina International's Scientific Newsletter, similarity:Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily., similarity:Contains 1 AGC-kinase C-terminal domain., similarity:Contains 1 C2 domain., similarity:Contains 1 protein kinase domain., similarity:Contains 2 phorbol-ester/DAG-type zinc fingers., subunit:Interacts with CDCP1.,