Database for Annotation, Visualization and Integrated Discovery 2.1
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Rho associated coiled-coil containing protein kinase 1(ROCK1) Rho associated coiled-coil containing protein kinase 1(ROCK1) Related Genes Homo sapiens
CHROMOSOME 18,
CYTOBAND 18p11.32, 18q11.1,
ENSEMBL_GENE_ID ENSG00000067900,
GENERIF_SUMMARY role in the control of cell shape and lymphocyte chemotaxis, Expressed in myometrium, ROCK-1 may contribute to pancreatic cancer cell invasion and/or metastasis by facilitating cancer cell migration, ROCK and Dia have opposing effects on adherens junctions downstream of Rho, The Rho-associated protein kinase p160ROCK is required for centrosome positioning., Activation of RhoA kinase promotes beta1 and beta2 integrin-dependent leukocyte de-adhesion by inhibiting cytoskeletal-dependent spreading, a new mechanism for regulation of integrin receptor avidity., dual function in human parturition, Continued disruption of the cytoskeletal microtubule ring, appears to be a Rhokinase-dependent event involved in the transformation of discoid platelets into spheres., Breast epithelial cells sense the rigidity or density of their environment via ROCK-mediated contractility and a subsequent down-regulation of Rho and FAK function, which is necessary for breast epithelial tubulogenesis to occur., ROCKI interacts with the switch regions of RhoA, invasiveness of hepatocellular carcinoma is facilitated by the Rho/Rho-kinase pathway is likely to be relevant to tumor progression, results indicate that remnant-like particles from sudden cardiac death patients upregulate Rho-kinase in coronary vascular smooth muscle cells and markedly enhance coronary vasospastic activity, RhoA, mDia, and ROCK have roles in cell shape-dependent control of the Skp2-p27kip1 pathway and the G1/S transition, Potassium chloride acts in part through stimulation of Rho and ROCK, possibly secondary to voltage-dependent Ca2+ influx., a novel nuclear export is activated by the ROCK signaling pathway to exclude hnRNP C1/C2 from nucleus, by which the compartmentalization of specific hnRNP components is disturbed in apoptotic c, epithelial cell motility is modulated by integrin engagment through RhoA/ROCK and PAK1, data suggest that statins exert their effects on shedding of sAPP(alpha) from cultured cells, at least in part, by modulation of the isoprenoid pathway and ROCK1, Enhanced activation of Rho kinase contributes to augmented contraction of the basilar artery to serotonin after subarachnoid hemorrhage., Rho-kinase inhibition may be of value in treating age-related erectile dysfunction., a Cdc42-MRCK signal mediates myosin-dependent cell motility and there is convergence between Rho and Cdc42 signalling, a pseudopodial-located RhoA/ROCK/p38/NHE1 signal module is regulated by Protein Kinase A gating and then regulates invasion in breast cancer cell lines, CD95 capping and the subsequent cellular polarization is a ROCK signaling-regulated process., These results suggest that Rho-kinase regulates the association of alpha-adducin and spectrin with the actin cytoskeleton in platelet activation., Hyperglycemia stimulates Rho-kinase activity via PKC- and oxidative stress-dependent pathways, leading to increased PAI-1 gene transcription, ROCK has a role in ischemia-induced endothelial dysfunction during stroke, two N-terminal regions interact to form a dimerization domain linking two kinase domains together, Our data suggested that p160ROCK was involved in ovarian cancer cell invasion and metastasis by facilitating cancer cell migration, and that p160ROCK might be a potential new effective target for preventing metastasis of ovarian cancer., Prostate-derived sterile 20-like kinase 2 (PSK2) regulates apoptotic morphology via C-Jun N-terminal kinase and Rho kinase-1, ERK-MAPK promotes endothelial cell survival and sprouting by downregulating Rho-kinase signaling., there is an alternative mechanism for the hypoxic induction of VEGF in colon cancer that does not depend upon HIF-1alpha but instead requires the activation of PI3K/Rho/ROCK and c-Myc, Rho kinase, myosin-II, and p42/44 MAPK are potentially important players in different aspects of bile canalicular lumen morphogenesis., A constitutively active dimeric human ROCK I (3-543) kinase domain was expressed in Sf-9 cells. We have identified a minimal functional subdomain of ROCK I that can be used in crystallization studies., Vascular endothelial growth factor (VEGF) elicits the activation of the VEGFR2-ROCK pathway, leading to phosphorylation of Ser732 within FAK which changes the conformation of FAK, making it accessible to Pyk2., Ability of MSCs to differentiate into neuron-like cells in response to CoCl(2), an effect that might act, in part, through HIF-1 activation and cell-cycle arrest, and which is potentiated by inhibition of ROCK., burst in presteady-state kinetics & viscosity effect on k(cat) of 1.3 +/- 0.2 characterize phosphoryl transfer step to be fast & release of product &/or enzyme isomerization step accompanying it as rate-limiting at V(max) conditions., cholesterol potentiates the Ca(2+) sensitization of VSM mediated by a SPC/Src-TK/Rho-kinase pathway, These results suggest that ROCK plays an essential role in the regulation of the intracellular mechanical response to VEGF of endothelial cells in a 3D matrix., Data suggest that Rho kinase-dependent contractile force generation leads to co-alignment of cells and collagen fibrils along the plane of greatest resistance, and that this process contributes to global matrix contraction, ROCK-1-dependent caspase-3 activation was coupled with the activation of PTEN and the subsequent inhibition of protein kinase B (Akt) activity, all of which was attenuated by siRNA directed against ROCK-1 expression., These results indicate that 2ME-induced barrier disruption is governed by microtubule depolymerization and p38- and ROCK-dependent mechanisms., The inhibition of Rho-Associated coiled-coil-containing protein kinase (ROCK), an activator of FAK, suppressed CAGE-promoted motility., ROCK1 is associated with the apoptosis-inducing effect of endogenous nitric oxide suppression in cancer cells., Adhesive and protrusive events involved in organized epithelial motility downstream of ROCK are separately coordinated through the phosphorylation of (respectively) myosin light chain and cofilin., Dual regulatory role for Rho kinase in fibroblast regulation in which lipid-induced Rho kinase activation suppresses fibroblast morphogenesis while TGF-beta1-induced Rho kinase activation culminates in transformation into myofibroblasts., Rho kinase mediates both early- and late-phase cold-induced vasoconstriction (VC) providing a putative mechanism through which both adrenergic and nonadrenergic cold-induced VC occurs in an in vivo human thermoregulatory model, Study demonstrates that the p53-mediated induction of RhoE in response to DNA damage favors cell survival partly through inhibition of ROCK I-mediated apoptosis., MLC2 phosphorylation is regulated by both ROCK and MLC kinase and plays an important role in platelet biogenesis by controlling proplatelet formation and fragmentation., findings report that the Notch1 gene is a p53 target in human keratinocytes with a role in tumor suppression of this cell type through negative regulation of the ROCK1/2 and MRCKalpha kinases, These data demonstrate a role for Anaplasma phagocytophilum-mediated ROCK1 phosphorylation in infection induced by PSGL-1 and mediated by Syk., These results indicate that Rho-kinase can directly phosphorylate eNOS at Thr495 to suppress nitric oxide production in endothelium., These results suggest the existence of a feedback loop between cytoskeletal tension, adhesion maturation, and ROCK signaling that likely contributes to numerous mechanochemical processes., ROCK I cooperates with RhoB to activate NF-kappaB, and suppression of ROCK I activity by genetic or pharmacological inhibitors blocks NF-kappaB activation., that ALIX and TSG101/ESCRT-I also bind a series of proteins involved in cytokinesis, including CEP55, CD2AP, ROCK1, and IQGAP1., plexin-B1 promotes endothelial cell motility through RhoA and ROK by regulating the integrin-dependent signaling networks that result in the activation of PI3K and Akt, results suggest that ROCK and ERK1/2 play more important roles than RhoA in PGE(2)-mediated migration stimulation of first-trimester trophoblasts., Members of the ROCK/Rho pathway act upstream from the kinase that phosphorylates P450c17 in a fashion that augments 17,20 lyase activity, possibly acting to catalyze a priming phosphorylation., PDK1 competes directly with RhoE for binding to ROCK1. In the absence of PDK1, negative regulation by RhoE predominates, causing reduced acto-myosin contractility and motility., ROCK, activated by G protein-coupled receptor ligands such as thrombin, directly phosphorylates FHOD1 at the C-terminal region, which renders this formin in the active form, leading to stress fibre formation., Inhibition of ROCK activity in human-derived cells enhanced either bacterial adhesion or adhesion and entry in an InlF-independent manner, further suggesting a host species or cell type-specific role for InlF., Permeability of cations in the alkali metal series was increased by PRLprolactin, and such increases were abolished by ROCK inhibitors., The expression of ROCK-1 was closely related to the invasion capability and migratory activity of ovarian cancer cells., RhoA/Rho-associated kinase signaling plays positive and negative roles in myogenic differentiation, mediated by MRTF-A/Smad-dependent transcription of the Id3 gene in a differentiation stage-specific manner, Rock1 and 2 are activated in response to wounding. ROCK activities enhance cell proliferation and epithelial differentiation, but negatively modulate cell migration and adhesion and therefore play a role in regulating corneal epithelial wound healing., Even though ROCK signaling plays a role in human trophoblast cell invasion, extravillous cytotrophoblastic cell migration can still occur in the absence of ROCK activity., Placenta growth factor directly regulates the motility of human lung cancer cells and that this regulation critically dependent on ROCK-1, DLC1 negatively regulates Rho/ROCK/MLC2, Rock potently stimulates the differentiation of resting fibroblasts into myofibroblasts and the production of extracellular matrix in scleroderma fibroblasts., the late failure of cytokinesis responsible for the endomitotic process is related to a partial defect in the Rho/Rock pathway activation, The Diaphanous-related Formin FHOD1 associates with ROCK1 and promotes Src-dependent plasma membrane blebbing., ROCKI and possibly ROCKII are key factors in regulation of motility/invasion of breast cancer cells., the signal initiated by thrombin bifurcates at the level of RhoA to promote changes in the cytoskeletal architecture through ROCK, and the remodeling of focal adhesion components through protein kinase C-related kinase, Prolonged androgen receptor (AR) localization to the regulatory regions of AR targeted genes and the recruitment of p160 coactivators are a potential mechanism leading to androgen-independent activation of the AR in prostate cancer., direct interaction between ROCK1 and LIMK2 in polarised but not blebbing cells; results point to a specific role for the ROCK1, a feedback loop between Rho/ROCK, Src, and phosphorylated Cav1 in tumor cell protrusions, identifying a novel function for Cav1 in tumor metastasis that may contribute to the poor prognosis of some Cav1-expressing tumors., Phosphorylation of ezrin/moesin by ROCK is involved in the early steps of apoptotic signaling following Fas receptor triggering and regulates apoptosis induction in Jurkat cells., mutation of the RhoE effector region attenuates RhoE-mediated disruption of the actin cytoskeleton, indicating that RhoE exerts its inhibitory effects on ROCK-I through protein(s) binding to its effector region., Rho-Associated Kinases is involved in Proton-Translocating ATPases /P2RY13 protein-mediated Lipoproteins, HDL endocytosis pathway., ROCK, a key downstream mediator of TGF-beta and other factors might become a unique therapeutic target in the treatment of proliferative vitreoretinal diseases., Rap1 as another downstream target of the Abl-CrkII signaling module and show that Abl-CrkII collaborates with Rho-ROCK1 to stimulate cell retraction., Upon UVB-induced stress in keratinocytes, ROCK1 was activated, bound to JIP-3, and activated the JNK pathway, ROCK1 and ROCK2 regulated myosin light chain phosphatase. ROCK isoforms had distinct and opposing effects on vascular smooth muscle cell (VSMC) morphology and ROCK2, but not ROCK1, had a predominant role in VSMC contractility., Rho mediates various phenotypes of malignant transformation by Ras and Src through its effectors, ROCK and mDia [review], Rho kinase activity is inhibited by HMG-CoA statins in patients with atherosclerosis, Inhibition of Rho-dependent kinases ROCK I/II activates VEGF-driven retinal neovascularization and sprouting angiogenesis., Both receptor-stimulated and steady-state Kv1.2 trafficking modulated by RhoA/ROCK required the activation of dynamin as well as the ROCK effector Lim-kinase, indicating a key role for actin remodeling in RhoA-dependent Kv1.2 regulation., We did not find association between studied SNPs of ROCK1 and schizophrenia in the Japanese population, Rho kinase-1 mediates cardiac fibrosis by regulating fibroblast precursor cell differentiation., Caov-3 cell growth was dependent on the Rho effector p160 Rho kinase, alpha2-integrin expression and Rho kinase activity are regulated by protein kinase signaling cascades upon activation of alpha7 nicotinic receptor, The increased expression of RhoA and Rho kinase in uterine smooth muscle may play an important role in the initiation of labor., Provide evidence for Rho-kinase activation in patients with pulmonary arterial hypertension., ROCK-mediated up-regulation of p21(Cip1) and the cytoskeleton in PKCdelta-dependent apoptosis in prostate cancer cells., These data suggest that ROCK1 and ROCK2 play distinct roles in regulating keratinocyte adhesion and terminal differentiation., These results demonstrate a new interaction that directly links ROCK to increased cartilage matrix production via activation of SOX9 in response to mechanical and growth factor stimulation, Results demonstrate a biphasic regulation of ROCK in response to adhesion, inhibition of ROCK initially and subsequently, re-activation is required for maturation of adhesion complexes and enhanced tumor cell migration., Data show that both lysophosphatidic acid and ROCK inhibition enhanced cell motility and that their combined effects significantly increased migration rate., Stduies indicate that cGMP-dependent protein kinase I modulates the RhoA-ROCK pathway and insulin receptor signaling to elicit BAT differentiation and stimulate thermogenesis., Helicobacter pylori disrupts gastric epithelial barrier structure via IL-1RI-dependent activation of ROCK, which in turn mediates tight junctional claudin-4 disruption., Rho-kinase regulates negatively EGF-induced cell proliferation upstream of Akt/GSK-3beta in colon cancer cells, [review] Rho-kinase is constitutively active in regulating vasoconstrictor tone in the pulmonary and systemic vascular bed and thus may have an important role in the pathogenesis of pulmonary hypertension., somatic ROCK1 mutations lead to elevated kinase activity and drive actin cytoskeleton rearrangements that promote increased motility and decreased adhesion, characteristics of cancer progression., activation of the RhoA-ROCK-p38MAPK-MSK signaling pathway is essential for the regulation of the phenotype and of the CST5/cystatin D candidate tumor suppressor and other target genes by 1,25(OH)2D3 in colon cancer cells, Data show that the Rho/ROCK signaling pathway may prove to be a promising target in anti-tumor therapy., Mutant PIK3CA interferes with apoptosis downstream of death receptor-signal complex, allowing caspase-8 activation without apoptosis. Cleavage of ROCK-1 by caspase-8 triggers amoeboid shape and invasiveness of HCT116 cells in response to TRAIL and CD95L., Heparin inhibits pulmonary artery smooth muscle cell proliferation through GEF-H1/RhoA/ROCK/p27 signaling pathway., Polarization and migration of hematopoietic stem and progenitor cells rely on the RhoA/ROCK I pathway and an active reorganization of the microtubule network., hHS-M(21) is a heart-specific effector of ROCK and plays a regulatory role in the MYPT1 phosphorylation at Thr-696 by ROCK, PHD2 affects cell migration and F-actin formation via RhoA/rho-associated kinase-dependent cofilin phosphorylation, the phospho myosin-binding subunit of ROCK has a role in cardiovascular disease, Rho proteins and ROK play a pivotal role in this signaling cascade, Studies indicate that inhibition of Rho-associated kinase (ROCK) decreased PTHrP expression., miR-584 is a new tumour suppressor miR in ccRCC and inhibits cell motility through downregulation of ROCK-1, The beneficial effects of simvastatin may be mediated by ROCK., In embryonic fibroblasts, protein levels of RhoA, ROCK1 and CTGF were up-regulated after 1.5 h of hypoxia and increased further with longer exposure to hypoxia., The genes identified KTN1, ROCK1, and ZAK may be responsible for loss of cellular homeostasis in giant cells tumors of bone, highly expressed in osteosarcoma; knockdown inhibits proliferation and induces apoptosis, ROCK and cAMP both promote lymphatic endothelial barrier function, however ROCK appears to also serve as a mediator of histamine and thrombin-induced barrier dysfunction, present the crystal structure of a large section of the central coiled-coil domain of human ROCK I (amino acids 535-700). The structure forms a parallel alpha-helical coiled-coil dimer that is structurally similar to tropomyosin, Expression levels of RhoC and ROCK-1 in prostate carcinoma are higher than those in corresponding paracancerous tissues, showing a significant positive correlation with distant metastasis., These data suggest that osteogenic growth peptide not only acts on bone marrow mesenchymal stem cells to stimulate osteogenic differentiation, but also in a dose-dependent manner, and this effect is mediated via the activation of RhoA/ROCK pathway., p120-catenin regulates growth of metastatic lobular carcinoma through Rock1-mediated anoikis resistance, show that cytokine signaling through the receptor subunit GP130-IL6ST and the kinase JAK1 generates actomyosin contractility through Rho-kinase dependent signaling, Rho-kinase signaling pathway plays a suppressive role in the intracellular vesicle trafficking of pEGFR via the endocytic pathway., We show constitutive activation of Rho kinase in cells bearing oncogenic forms of KIT, FLT3, and BCR-ABL, which is dependent on PI3K and Rho GTPase., Inhibition of the ROCK pathway restored the ability of gamma-actin-knockdown cells to migrate. This demonstrates gamma-actin as a potential upstream regulator of ROCK mediated cell migration., ROCK1 may play a role in the development of albuminuria in diabetic kidney disease by downregulating the endocytosis receptors complex - megalin/cubilin., Results show an inverse correlation between miR-148a and ROCK1 expression in gastric cancer tissues., 14-3-3 proteins mediate CaR-dependent Rho signalling and may modulate the plasma membrane expression of the CaR., p120 dynamically regulates Rho-GTPase activity at the E-cadherin complex through transient interaction with several of its up- and downstream effectors, including ROCK1, Fasudil can reduce the secretion of downstream inflammatory factors and cytokines by inhibiting high glucose-activated HMCs Rho/ROCK signaling pathway in mesangial cells., MYBPH inhibited assembly competence-conferring phosphorylation of the myosin regulatory light chain (RLC) as well as activating phosphorylation of LIM domain kinase, unexpectedly through its direct physical interaction with Rho kinase 1., ROCK1 has a role in regulating myometrial contractility., These results clearly suggested that the Rho/ROCK is a potent primary effector of mechanical stress in the pluripotent stem cells and it participates to pluripotency-related signaling cascades as an upper stream regulator., Results demonstrate differential effects of Snail and Slug in pancreatic cancer and identify the interplay between Rho signaling and beta1-integrin that regulates the scattering and migration of Snail- and Slug-expressing pancreatic cancer cells., LIMK1 and LIMK2, the downstream effectors of RhoA and ROCK, regulate centrosome integrity and astral microtubule organization, respectively., ROCK1 and ROCK2 have distinct and separate roles in adhesion complex assembly and turnover in human epidermal keratinocytes., Matrix-associated PAI-1 plays a role in the cell behavior needed for amoeboid migration by maintaining cell blebbing, localizing PDK1 and ROCK1 at the cell membrane and maintaining the RhoA/ROCK1/MLC-P pathway activation., We conclude that ROCK proteins are necessary for acquisition of elongated and geometric cell shape, two key events for epithelial differentiation., The structure of Shrm domain 2 (SD2), which mediates the interaction with Rock and is required for Shrm function, is reported., analysis of the mechanism for negatively regulating Rho-kinase (ROCK) signaling through Coronin1B protein in neuregulin 1 (NRG-1)-induced tumor cell motility, Inhibition of ROCK by Y-27632 inhibited the activity of RhoA and promoted the apoptosis of gastric cancer cells., our overall results reveal a model whereby CD1d-mediated Ag presentation is negatively regulated by ROCK1 and ROCK2 via its effects on the actin cytoskeleton., Rho-kinase activation is substantially involved in the pathogenesis of the DES-induced coronary hyperconstricting responses in patients with CAD, suggesting the therapeutic importance of Rho-kinase pathway., Crystal structures of the RKI-1447/ROCK1 complex revealed that RKI-1447 is a Type I kinase inhibitor., ROCK1-positive fibroblasts were also identified by immunohistochemistry in the alveolar parenchyma in lung tissue sections from COPD patients, Increased Rho kinase activity predicted worse cardiovascular outcome in patients with acute coronary syndrome., suppression of ROCK1 or ROCK2 expression alone was sufficient to impair anchorage-independent growth, supporting their nonoverlapping roles in oncogenesis, Inhibition of ROCK1 during the starvation period led to a more rapid response with the production of larger early autophagosomes that matured into enlarged late degradative autolysosomes., the two isoforms of Rho-kinase distribute differentially to accomplish their specific functions, RhoA is a PKGIalpha target and direct binding of activated PKGIalpha to RhoA is central to cGMP-mediated inhibition of the VSMC Rho kinase contractile pathway, DEX interferes with the adhesion function of U937 cells through the inhibition of ROCK1 activity, Data indicate that phosphorylation of FilGAP by ROCK appears to promote amoeboid morphology., Rho-associated protein kinase and Wnt signaling regulates Mypt1 and Nkx2.5 colocalization outside the cell nucleus., NDRG1 inhibited an important regulatory pathway mediated by ROCK1/pMLC2 pathway that modulates stress fiber assembly., miR-148b controls malignancy by coordinating a novel pathway involving over 130 genes and, in particular, it directly targets players of the integrin signaling, such as ITGA5, ROCK1, PIK3CA/p110alpha, and NRAS, as well as CSF1, Positive rates of Rac1, Pak1 and Rock1 expression in normal tissue, dysplasia and gastric carcinoma show an increasing trend and are correlated with tumor lymph node metastasis and TNM stage., Our data showed that the ROCK1 and ROCK2 genes might be a risk factor for colorectal cancer development, Rapid secretion of TSP-1 from MDA-MB-231 cells depends on ROCK1 inhibition., dual Rock and Cdk phosphorylation of Tppp1 inhibits its regulation of the cell cycle to increase cell proliferation, Sulfide induces both ROCK-1 and ROCK-2 cleavage and causes ROCKdependent cell blebbing during apoptosis., Results suggest miR-126 function as a potential tumor suppressor in colon cancer progression and miR-126/RhoA/ROCK may be a novel candidate for developing rational therapeutic strategies., CCR4 mediates CCL17 induced cell migration via increased total RhoA and active RhoA protein levels in colon cancer cells., These findings indicate that Rho-kinase regulates ER stress-mediated VCAM-1 induction by ATF4- and p38MAPK-dependent signaling pathways., Data indicate that knockdown of ROCK1 reversed epithelial-to-mesenchymal transition (EMT) resembling that of miR-148a overexpression., Data indicate that Epac1-Rap1A-RhoA-ROCK signaling affects Cl- secretion via effects on the apical expression of KCNN4c channels., Exposure of smooth muscle cells to apo(a) in migration assays induced a potent, concentration-dependent chemorepulsion that was RhoA and integrin alphaVbeta3-dependent, but transforming growth factor beta-independent., Ostf1b could constitutively activate the Rho kinase 1 (ROCK1) and myosin light chain 2 (MLC2) signalling pathway that promotes cell migration, epithelial mesenchymal transition (EMT) and cytoskeletal dynamics through stress fibre formation., Androgen receptor might play a negative role during prostrate cancer progression via influencing entosis by modulating Rho/ROCK. pathway., Low frequency intermediate penetrance (LFIP) variants in the ROCK1 gene predispose to the risk of TOF, Immunohistochemical and western blot analyses showed no change in ROCK1 and ROCK2 protein expressions in Barrett's esophagus, The RhoA/ROCK1 signalling pathway has important roles in the determination of cell fate., miR-340 acts as a tumor suppressor and its downregulation in tumor tissues may contribute to the progression and metastasis of OS through a mechanism involving ROCK1, ROCK1 acts as a prominent upstream regulator of Beclin1-mediated autophagy and maintains a homeostatic balance between apoptosis and autophagy., These results revealed a novel mechanism that miR-124 inhibits glioma cells migration and invasion via ROCK1 downregulation., Results suggest that Aurora B, but not Rho/MLCK (myosin-light-chain kinase) signaling, is essential for the localization of 2P-MRLC (myosin regulatory light chains) to the midzone in dividing HeLa cells., ROCK1 was negatively regulated by miR-335 at the posttranscriptional level, via a specific target site within the 3'UTR by luciferase reporter assay., Intracellular forms of NOTCH1 trigger the immediate activation of ROCK1 independent of its transcriptional activity, promoting differentiation and resulting in decreased clonogenicity of normal human keratinocytes., it is suggested ROCK1 phosphorylates and activates SOX9 in Sertoli cells. Testes formation might be initiated by an alternative signaling pathway attributed to ROCK1, not SRY, activation in XX testes., Active ROCKI is phosphorylated at Ser1333 site. Antibodies that recognize phospho-Ser1333 of ROCKI and phospho-S1366 residues of ROCKII offer a means to discriminate their individual active status in cells and tissues., ROCK1 deletion altered the substrate-dependent cell migration in glioblastoma cells., miR-124-3p can repress the migration and invasion of bladder cancer cells via regulating ROCK1, IKKgamma facilitates RhoA activation via a guanine nucletotide exchange factor, which in turn activates ROCK to phosphorylate IKKbeta, leading to NF-kappaB activation that induced the chemokine expression and cell migration upon TGF-beta1., This study demonistrated by Gene expression profile that ROCK1 upregulaion in fibroblasts of Huntington's disease patients., A systematic review of RhoA/ROCK blockade approaches analyzes the impact of bias that may lead to inflated effect sizes and functional locomotor recovery after experimental thoracic spinal cord injury., ROCK has a crucial role in regulating prostate tumor growth through interaction with c-Myc, RACK1, by acting as a component of the IKK signalosome, plays a key role in inhibiting IKK activity by interfering with TRAF2-mediated recruitment of the IKK complex., coordinated RhoA-ROCK1 expression and signaling are mediated by hypoxia-inducible factors in breast cancer cells, results demonstrated that p38 and ERK1/2 played crucial positive roles in adipogenesis, and FAK, RhoA/ROCK and cytoskeleton played negative roles, ROCK1 upregulation occurred more frequently in osteosarcoma tissues with positive metastasis and poor response to pre-operative chemotherapy., RhoC/ROCK1 signaling pathways are likely involved in the progression of cervical squamous cell carcinoma, MicroRNA 135a suppresses lymph node metastasis through down-regulation of ROCK1 in early gastric cancer., ROCK-1 protein plays a key role in regulating metastasis and invasion of retinoblastoma cells., This is the first study to show that ROCK1 gene polymorphisms may have a significant impact on susceptibility to BD., ROCK1, as a novel target of miR-145, acts as a positive regulator of glioma cell invasion. Therefore, ROCK1 may constitute a promising target for glioma treatment., An mDia2/ROCK signaling axis regulates invasive egress from epithelial ovarian cancer spheroids., This is the first study to examine the involvement of ROCK1 and ROCK2 gene variations in the risk of primary open-angle glaucoma development., ROCK1- and LIMK1-regulated phosphorylation of cofilin played a role in retrovirus release from host cells and in cell-cell transmission events., It regulates relaxation of vascular smooth muscle., miR-145 may act as a tumor suppressor and contributes to the progression of OS through targeting ROCK1., Data indicate that Rho-associated protein kinase 1 (ROCK1) was inversely correlated with miR-186 expression in non-small cell lung cancer (NSCLC)., Data indicate that dexamethasone inhibition of Rho-associated coiled-coil-containing protein kinase 1 (ROCK1) activity involved Ras homolog family member A (RhoA)-independent signaling pathways., Data suggests that the rho-associated protein kinase (ROCK)-focal adhesion kinase (p-FAK cascade plays an important role in the effect of caffeine in glioma cells., silencing of ROCK1 suppressed cell proliferation, migration, and invasion, while supplementation of ROCK1 remarkably restored the cell growth and invasion inhibited by miR-124., The differential expression of ROCK-1 and MMP-9 proteins suggests their potential use as prognostic markers in breast cancer., aberrant modulation of Rock1 expression and activity induced by ITD-FLT3 may enhance acute myeloid leukemia cell chemotaxis to the therapy-protective bone marrow niche, where Cxcl12 is abundantly expressed, The expressions of ROCK1 in glioma tissue were visibly upregulated and the increase of ROCK1 had a positive correlation with the malignant grade of glioma., ROCK1 is lower expressed in tumour tissue when compared with adjacent normal vulvar epithelia. In an independent sample set of VSCCs, lower expression levels of ROCK1 correlated with worse survival rates and a poor prognosis., FRMD5 regulates tumor cell motility via a dual pathway involving FRMD5 binding to integrin beta5 tail and to ROCK1, Sep15 in Chang liver cells regulates the pathway that antagonizes RhoA/ROCK/MLC-dependent non-apoptotic bleb formation., We identified ROCK1 as a potential drug target for BRAF mutant melanoma. ROCK1 silencing increased melanoma cell elimination when combined with BRAF or ERK inhibitor treatment., inhibition of p38 MAP kinase attenuated the histamine response in all three EC types. Inhibition of RhoA, ROCK, or MLCK also prevented the histamine-induced decrease in TER in HDMEC., Depletion of the kinases ROCK1 and ROCK2, two known RhoC downstream effectors, similarly decreases cancer interaction with ECs, ROCK1 and ZIPK have diverse, but predominantly distinct regulatory functions in vascular SMC and that ROCK1-mediated activation of ZIPK is not involved in most of these functions., Our data indicate that expression of ROCK1 and ROCK2 are closely associated with tumor growth and lymph node metastasis of laryngeal squamous cell carcinoma, Our data revealed that miR-335 could inhibit the proliferation and migration invasion of HCC cells via regulating ROCK1, suggesting that miR-335 could be a therapeutic biomarker of HCC in the future, ROCK1 was validated as a direct functional target miR-340 and silencing of ROCK1 phenocopied the anti-tumor effect of mR-340., These data on the role of RhoA/ROCK in regulating cell myogenic differentiation on lasered microchannels substrates may provide a mechanistic insight on human mesenchymal stem cells fate directed by substrate topography., our data suggest that inhibition of ROCKRho-kinases ROCK 1 and ROCK 2) reduces the ability of melanoma cells to efficiently colonize the lungs, miR-144 suppresses OS progression by directly downregulating ROCK1 and ROCK2 expression., These results indicate that bleb formation is dependent on Rho activity (ROCK1 and ROCK 2)in ouabain-induced cell death in HUVECs, RNA interference (RNAi) screen in primary leukemic cells. Stringent validation identified 6 genes (BNIPL1, ROCK1, RPS13, STK3, SNX27, WDHD1) whose knockdown impaired growth and viability of the cells., 17beta-estradiol induces proliferation of uterine smooth muscle cells in endometriosis through hyperactivation of the estrogen receptor-RhoA/ROCK signaling pathway., miR-124 promotes hyperplasia and contributes to invasion of colorectal cancer cells, but downregulates ROCK1., ROCK I provides better efficacy in predicting patient outcomes, compared to either tumor staging or MET expression., results indicate that the two SNPs (Cav-1 rs1049334 and ROCK1 rs35996865) and genotypes with a combination of 2-4 risk alleles were associated with the risk of ccRCC., miR144 acts as a tumor suppressor by targeting ROCK1 in osteosarcoma., The RhoA/ROCK signalling pathway has a key role in Ca2+ sensitisation in smooth muscle., miR-146a has a critical role in the process of androgen-independent prostate cancer cells apoptosis through regulation of ROCK/Caspase 3 pathway., These results indicate that miR-584 could inhibit the expression of ROCK1, and ROCK1 knockdown would further affect the migration ability of K1 cells., Together, the data of the present study demonstrated that miR144 acts as a tumor suppressor by targeting ROCK1, and indicates the potential of miR144 as a novel biomarker and target in the treatment of rectal cancer., We speculate that the drop of the ROCK-to-MLCK ratio may occur as an attempt to compensate for the increased Rho kinase activity., findings collectively suggest that miR-506 acts as a tumor suppressor via regulation of ROCK1 expression and may thus be a promising therapeutic target for HCC, ROCK activity in MS serum was elevated compared with serum from healthy controls, We conclude that 2-ME inhibits the pathway RhoA --> ROCK1 --> myosin phosphatase targeting subunit --> myosin light chain, and this likely contributes to the reduced cytokinesis in 2-ME treated HASMCs., miR148b directly targets Rhoassociated protein kinase 1 in hepatocellular carcinoma., the ROCK1 rs35996865 G variant allele was significantly more frequent in male colorectal cancer (CRC) patients (p = 0.028) than in the control group; finding points to a possible gender-related modulation by the ROCK1 gene in CRC susceptibility, This study report that protein levels of the Rho-associated protein kinases (ROCK1) was increased in Progressive Supranuclear Palsy and Corticobasal Degeneration brains., Increased ROCK activity was found in chronic kidney disease patients with left ventricular hypertrophy., These findings suggested that miR-198 may act not only as a novel prognostic marker, but also as a potential target for molecular therapy of osteosarcoma., Galectin-9 stimulated migration in human NK-92 cells by affecting F-actin polarization through the Rho/ROCK1 signaling pathway., New light on the role of the ROCK pathway during early stages of human neurogenesis.,
SP_COMMENT catalytic activity:ATP + a protein = ADP + a phosphoprotein., domain:The C-terminal auto-inhibitory domain interferes with kinase activity. RHOA binding leads to a conformation change and activation of the kinase. Truncated ROCK1 is constitutively activated., enzyme regulation:Activated by RHOA binding., function:Protein kinase that phosphorylates a large number of important signaling proteins, and thereby regulates the assembly of the actin cytoskeleton, cell migration, invasiveness of tumor cells, smooth muscle contraction and neurite outgrowth. Necessary for apoptotic membrane blebbing. Plays a role in smooth muscle contraction. Required for centromere positioning and centromere-dependent exit from mitosis., miscellaneous:Inhibited by Y-27632., PTM:Autophosphorylated on serine and threonine residues. Phosphorylated upon DNA damage, probably by ATM or ATR., PTM:Cleaved by caspase-3 during apoptosis. This leads to constitutive activation of the kinase and membrane blebbing., similarity:Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family., similarity:Contains 1 AGC-kinase C-terminal domain., similarity:Contains 1 PH domain., similarity:Contains 1 phorbol-ester/DAG-type zinc finger., similarity:Contains 1 protein kinase domain., similarity:Contains 1 REM (Hr1) repeat., subcellular location:Associated with the mother centriole and an intercentriolar linker (By similarity). A small proportion is associated with Golgi membranes., subunit:Binds RHOA (activated by GTP). Interacts with ADD1, GEM, RHOB, RHOC, MYLC2B and VIM (By similarity). Binds RHOE, PPP1R12A, LIMK1 and LIMK2. Interacts with TSG101., tissue specificity:Detected in blood platelets.,
Rho associated coiled-coil containing protein kinase 2(ROCK2) Rho associated coiled-coil containing protein kinase 2(ROCK2) Related Genes Homo sapiens
CHROMOSOME 2,
CYTOBAND 2p24,
ENSEMBL_GENE_ID ENSG00000134318,
GENERIF_SUMMARY kinetic mechanisms, ROCK-II-induced membrane blebbing and chromatin condensation require actin cytoskeleton. "ROCK-II", characterization and purification of human ROCK-II, diphosphorylated MRLC and Rho-kinase accumulated and colocalized at the contractile ring and the midbody in dividing cells, ROKalpha is regulated by CRMP-1 and CRMP2, results indicate that remnant-like particles from sudden cardiac death patients upregulate Rho-kinase in coronary vascular smooth muscle cells and markedly enhance coronary vasospastic activity, Data show that granzyme B directly cleaves ROCK II, and that this causes constitutive kinase activity and bleb formation., The crystal structure of an active Rho-kinase fragment containing the kinase domain revealed a head-to-head homodimer through the N-terminal extension forming a helix bundle that structurally integrates the C-terminal extension., Common variation in ROCK2 exerts systemic resistance-mediated changes in blood pressure and is novel mechanism for human circulatory control and suggests new possibilities for diagnosis and treatment of subjects at risk of hypertension., study investigated the role of RhoA and Rho-kinase in endothelial eNOS protein expression under hypoxic conditions, These results indicate that 2ME-induced barrier disruption is governed by microtubule depolymerization and p38- and ROCK-dependent mechanisms., Dual regulatory role for Rho kinase in fibroblast regulation in which lipid-induced Rho kinase activation suppresses fibroblast morphogenesis while TGF-beta1-induced Rho kinase activation culminates in transformation into myofibroblasts., findings report that the Notch1 gene is a p53 target in human keratinocytes with a role in tumor suppression of this cell type through negative regulation of the ROCK1/2 and MRCKalpha kinases, Plk1 and RhoA function to enhance Rock2 kinase activity in vitro and within cells, and implicate Plk1 as a regulator of multiple pathways that synergistically converge to regulate actomyosin ring contraction during cleavage furrow ingression., These findings demonstrate a central role of the GEF-H1/Rho/ROCK-II signaling pathway in the disassembly of apical junctional complex in epithelial cells., Inhibition of ROCK activity in human-derived cells enhanced either bacterial adhesion or adhesion and entry in an InlF-independent manner, further suggesting a host species or cell type-specific role for InlF., Rock1 and 2 are activated in response to wounding. ROCK activities enhance cell proliferation and epithelial differentiation, but negatively modulate cell migration and adhesion and therefore play a role in regulating corneal epithelial wound healing., Rock potently stimulates the differentiation of resting fibroblasts into myofibroblasts and the production of extracellular matrix in scleroderma fibroblasts., ROCKI and possibly ROCKII are key factors in regulation of motility/invasion of breast cancer cells, a feedback loop between Rho/ROCK, Src, and phosphorylated Cav1 in tumor cell protrusions, identifying a novel function for Cav1 in tumor metastasis that may contribute to the poor prognosis of some Cav1-expressing tumors., a major haplotype block at the ROCK2 locus is recessively associated with a lower risk of hypertension, ROCK2 activity and dimerization were dependent upon the interaction between Thr(405) of the hydrophobic motif and Asp(39) of the N-terminal extension. The reciprocal exchange of these residues was permissive for kinase activity, but not for dimerization., ROCK1 and ROCK2 regulated myosin light chain phosphatase. ROCK isoforms had distinct and opposing effects on vascular smooth muscle cell (VSMC) morphology and ROCK2, but not ROCK1, had a predominant role in VSMC contractility., Inhibition of Rho-dependent kinases ROCK I/II activates VEGF-driven retinal neovascularization and sprouting angiogenesis., overexpressed in hepatocellular carcinoma and played a significant role in regulating cytoskeletal events and contributed to the invasion of hepatocellular carcinoma, Stimulation of PKC disrupts epithelial apical junctions via ROCK-II dependent stimulation of actomyosin contractility., Data conclude that common genetic variation in ROCK2 is unlikely to make a major contribution to the risk of pre-eclampsia, but cannot exclude the possibility of having missed non-coding functional variants or rare coding variants., Provide evidence for Rho-kinase activation in patients with pulmonary arterial hypertension., These data suggest that ROCK1 and ROCK2 play distinct roles in regulating keratinocyte adhesion and terminal differentiation., Pharmacologic inhibition of Rho kinase 2 signaling blocked LPA-induced p65 phosphorylation and suppressed ICAM-1 and VCAM-1 expression., A functional proteomics approach enabled the authors to identify novel LOX-1 interactors that potentially contribute to the cellular and signaling functions of LOX-1., results suggest that miR-138 plays an important role in TSCC cell migration and invasion by concurrently targeting RhoC and ROCK2, and miR-138 may serve as a novel therapeutic target for TSCC patients at risk of metastatic disease, Results suggest that VEGF-C promoted cervical cancer metastasis by upregulation and activation of moesin protein through RhoA/ROCK-2 pathway., upregulated rho-associated protein kinase 2, p-cofilin and intracellular adhesion molecule-1, and downregulated E-cadherin were found in esophageal squamous cell cancer cells, Thr431Asn polymorphism of the ROCK2 gene could be a risk factor for the metastases of the breast cancer, and may help in predicting the prognosis., Expression of miR-139 is reduced in human metastatic hepatocellular carcinoma samples and correlates with prognosis. The microRNA miR-139 interacts with ROCK2 and reduces its expression in hepatocellular carcinoma., The results of this study suggested that there were no evidence for an association of ROCK2 gene Thr431Asn and Arg83Lys polymorphisms with diabetes or diabetic retinopathy in the Turkish population., results suggested that a complex consisting of BRCA2, NPM, and ROCK2 maintains the numerical integrity of centrosomes and accurate cell division and that dysfunction of this regulation might be involved in the tumorigenesis of breast cancer, LR11 is phosphorylated in vivo and indicate that ROCK2 phosphorylation of LR11 may enhance LR11 mediated processing of APP and amyloid production., Ras/Raf/MAPK and RhoA/ROCKII signalling pathways are abnormally activated in eutopic endometrial stromal cells of patients with endometriosis, A novel mechanism for controlling ROCKII localization at the membrane, in which the ROCKII C-terminus acts as a coincidence detector for spatial regulatory signals., The up-regulated expression of ROCK2 is correlated with patient age and differentiation grade of esophageal squamous cell carcinoma., ROCK1 has a role in regulating myometrial contractility., Results demonstrate differential effects of Snail and Slug in pancreatic cancer and identify the interplay between Rho signaling and beta1-integrin that regulates the scattering and migration of Snail- and Slug-expressing pancreatic cancer cells., It was concluded that RhoA/ROCK is active in the internal anal sphincter (IAS), and is the critical determinant of the basal tone in intact human IAS and that they are potential therapeutic targets for a number of rectoanal motility disorders., We found that the extent of Ser1366 phosphorylation of endogenous ROCKII is correlated with that of myosin light chain phosphorylation in cells in response to RhoA stimulation, showing that Ser1366 phosphorylation reflects its kinase activity, ROCK1 and ROCK2 have distinct and separate roles in adhesion complex assembly and turnover in human epidermal keratinocytes., We conclude that ROCK proteins are necessary for acquisition of elongated and geometric cell shape, two key events for epithelial differentiation., A new role for Rock2 in modulation of Cdc25A ubiquitination has been revealed, indicating a novel mechanism of Cdc25A regulation and a potential function for Rock2 in the development of hepatocellular carcinoma., our overall results reveal a model whereby CD1d-mediated Ag presentation is negatively regulated by ROCK1 and ROCK2 via its effects on the actin cytoskeleton., Angiotensin II induces the contraction of airway smooth muscle cells; this effect can be reversed by Ang-(1-7), partially through the downregulation of of the RhoA/ROCK2 signaling pathway., The results strongly suggest that ROCK2 gene polymorphisms may modify individual susceptibility to Behcet's disease in the Turkish population., suppression of ROCK1 or ROCK2 expression alone was sufficient to impair anchorage-independent growth, supporting their nonoverlapping roles in oncogenesis, the two isoforms of Rho-kinase distribute differentially to accomplish their specific functions, These results suggest that ROCK2 might mediate bFGF-induced proliferation of SH-SY5Y cells through GSK-3beta and beta-catenin pathway, The relationship between the ROCK2 polymorphisms and cardiovascular disease risk cannot be entirely discounted and warrants further evaluation in a large population., Our data showed that the ROCK1 and ROCK2 genes might be a risk factor for colorectal cancer development, Sulfide induces both ROCK-1 and ROCK-2 cleavage and causes ROCKdependent cell blebbing during apoptosis., Results suggest miR-126 function as a potential tumor suppressor in colon cancer progression and miR-126/RhoA/ROCK may be a novel candidate for developing rational therapeutic strategies., we have shown that forced expression of wild-type CD99 in osteosarcoma cells induces downregulation of genes such as ROCK2, Immunohistochemical and western blot analyses showed no change in ROCK1 and ROCK2 protein expressions in Barrett's esophagus, CRMP-2-dependent regulation of ROCK II activity is mediated through interaction of the CRMP-2L N terminus with the ROCK II catalytic domain as well as by GSK3-dependent phosphorylation of CRMP-2., Testosterone induces actin cytoskeleton remodeling by regulating ROCK-2/moesin expression and activation., ROCK2 in vascular smooth cells contributes to the pathogenesis of hypoxia-induced pulmonary arterial hypertension., Active ROCKI is phosphorylated at Ser1333 site. Antibodies that recognize phospho-Ser1333 of ROCKI and phospho-S1366 residues of ROCKII offer a means to discriminate their individual active status in cells and tissues., Selective knockdown of ROCK2 exerted antidromic effects on glioma migration., Loss of TSC2 expression can alter microtubule organization and dynamics, which, in turn, deregulate cell division and potentially impair neuronal differentiation via ROCK2 signaling., ROCK2 gene Thr431Asn polymorphism is not a risk factor for migraine in the Turkish population., Study reports a unique, PGE2-induced, functional inhibitory phosphoS1379 site on ROCK2 that mutational analysis con fi rms is critical to the activity of the enzyme in terms of myosin light chain II and paxillin phosphorylation, hence controlling the formation of stress fi bres and focal adhesions in fibroblast-myo fi broblast transitions., morgana causes PTEN destabilization, by inhibiting ROCK activity, This is the first study to examine the involvement of ROCK1 and ROCK2 gene variations in the risk of primary open-angle glaucoma development., These results suggest that there is no association of the ROCK2 gene Thr431Asn polymorphism with the development of cardiac septal defects in pediatric patients., ROCK-II was activated in various lung cells of patients with idiopathic pulmonary fibrosis along with oxidative stress detected by 8-isoPGF2alpha elevation., protein kinase (ROCK)-focal adhesion kinase (p-FAK cascade plays an important role in the effect of caffeine in glioma cells., upregulation of MMP2 rescued the decreased migration and invasion induced by the knockdown of Rock2, whereas the knockdown of MMP2 decreased Rock2-enhanced hepatocellular carcinoma migration and invasion, miR-200b and miR-200c are suppressed in AGE-induced endothelial cell injury, resulting in unregulated RhoA/ROCK2 signaling., Two functional single nucleotide polymorphisms of ROCK2 increase susceptibility of arterial stiffness in the Chinese population., ROCK2 is required for CXCL8 responses by TNF-alpha stimulated IEC by affecting intracellular signaling through MKK4 adn JNK., Depletion of the kinases ROCK1 and ROCK2, two known RhoC downstream effectors, similarly decreases cancer interaction with ECs, Our data indicate that expression of ROCK1 and ROCK2 are closely associated with tumor growth and lymph node metastasis of laryngeal squamous cell carcinoma, Data indicate that dysfunction of the Rho-associated kinase 2 (Rock2)-p-GSK3beta/beta-catenin-CCAAT/enhancer-binding protein delta (CEBPD) regulatory circuitry may contribute to the tumorigenic characteristic of hepatocellular carcinoma (HCC)., our data suggest that inhibition of ROCK (Rho-kinases ROCK 1 and ROCK 2)reduces the ability of melanoma cells to efficiently colonize the lungs, ROCK2 is pivotal to baseline junctional tension as a novel mechanism by which Rho kinase primes the endothelium for hyperpermeability responses., knockdown of TMEM45A also inhibited cell adhesion as well as cell invasion. More importantly, suppression of TMEM45A notably downregulated the expression of TGF-b1, TGF-b2, RhoA and ROCK2., Results demonstrated that the miR-200b/200c/429 subfamily inhibited HCC cell migration through modulating Rho/ROCK mediated cell cytoskeletal reorganization and cell-substratum adhesion., miR-144 suppresses OS progression by directly downregulating ROCK1 and ROCK2 expression., These results indicate that bleb formation is dependent on Rho activity (ROCK1 and ROCK 2)in ouabain-induced cell death in HUVECs, 17beta-estradiol induces proliferation of uterine smooth muscle cells in endometriosis through hyperactivation of the estrogen receptor-RhoA/ROCK signaling pathway., miR-448 may contribute to the progression of Hepatocellular Carcinoma via regulating ROCK2 expression., Esophageal squamous cell carcinoma showed a positive expression of Rock2, which was significantly association with ethnic background., We speculate that the drop of the ROCK-to-MLCK ratio may occur as an attempt to compensate for the increased Rho kinase activity., ROCK activity in MS serum was elevated compared with serum from healthy controls, beta-catenin/TCF4 pathway contributed to the effects of Rock2 in CRC cells, and Rock2 stabilized beta-catenin by preventing its ubiquitination and degradation, no differences in renal interstitial fibrosis or UUOinduced ROCK activity were identified between the ROCK2 heterozygote knockout and WT mice, indicating that the genetic partial disruption of ROCK2 is insufficient for protecting against renal fibrosis., ROCK2 forms a dimer, 120 nm in length, with a long coiled-coil tether linking the kinase and membrane-binding domains., Study shows that nuclear ROCKII activation signal might contribute to the tumor metastasis in breast cancer., This study report that protein levels of the Rho-associated protein kinases (ROCK2) was increased in Progressive Supranuclear Palsy and Corticobasal Degeneration brains., Rho Kinase ROCK2 Mediates Acid-Induced NADPH Oxidase NOX5-S Expression in Human Esophageal Adenocarcinoma Cells,
SP_COMMENT catalytic activity:ATP + a protein = ADP + a phosphoprotein., enzyme regulation:Activated by RHOA binding., function:Protein kinase that phosphorylates a large number of important signaling proteins, and thereby regulates the assembly of the actin cytoskeleton. Promotes formation of stress fibers and of focal adhesion complexes. Plays a role in smooth muscle contraction., miscellaneous:Inhibited by Y-27632., PTM:Phosphorylated upon DNA damage, probably by ATM or ATR., similarity:Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family., similarity:Contains 1 AGC-kinase C-terminal domain., similarity:Contains 1 PH domain., similarity:Contains 1 phorbol-ester/DAG-type zinc finger., similarity:Contains 1 protein kinase domain., similarity:Contains 1 REM (Hr1) repeat., subcellular location:Cytoplasmic, and associated with actin microfilaments and the plasma membrane., subunit:Homodimer. Binds RHOA that has been activated by GTP binding. Binds IRS1, RHOB and RHOC.,