Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
The Database for Annotation, Visualization and Integrated Discovery
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Raf-1 proto-oncogene, serine/threonine kinase(RAF1) Raf-1 proto-oncogene, serine/threonine kinase(RAF1) Related Genes Homo sapiens
CHROMOSOME 3,
CYTOBAND 3p25,
ENSEMBL_GENE_ID ENSG00000132155,
GENERIF_SUMMARY These data show that Ser-259 dephosphorylation contributes to Raf-1 activation by supporting its membrane accumulation rather than by increasing the specific activity of the kinase, PAK1 primes MEK1 for phosphorylation by Raf-1 kinase during cross-cascade activation of the ERK pathway., targeted expression inhibits juvenile myelomonocytic leukemia cell growth, effects of paclitaxel on Raf-1 phosphorylation in ovarian cancer cells, Results indicate that the phosphorylation of Ser(338) and Tyr(341) on Raf-1 exerts an important effect on reconfiguring the two MEK1-binding sites., These data suggest that GILZ contributes, through protein-to-protein interaction with Raf-1 and the consequent inhibition of Raf-MEK-ERK activation, to regulating the MAPK pathway and to providing a further mechanism underlying GCH immunosuppression., Raf activation increased the expression of cyclin A, cyclin D, cyclin E, and p21(Cip1), which are associated with G(1) progression, Activation of the ras/raf-1 signal transduction pathway leads to prominent phenotypic changes that resemble differentiation of gastrointestinal carcinoid cells in vitro., phosphorylation by p21-activated kinase 1 and Src regulates Raf-1 autoinhibition, c-Raf1 activation occurs without serine 338 phosphorylation, serum stimulation of fibroblasts in floating matrices does not result in ERK translocation to the nucleus and there was decreased serum activation of upstream members of the ERK signaling pathway, MEK and Raf., The 1,25(OH)(2)D3-responsive element in cystatin A gene is identical to TRE, T2 (-272 to -278). Suppression of Raf-1/MEK1/ERK1,2 signaling pathway increases cystatin A expression of normal human keratinocytes., Raf1 may have a role in antineoplastic drug resistance, Sprouty4 binds to Raf1 through its carboxy-terminal cysteine-rich domain, and this binding is necessary for the inhibitory activity of Sprouty4., findings implicate Raf-1 as a pivotal regulator of endothelial cell survival during angiogenesis, results show that raf-1 protein induction suppresses neuroendocrine marker and hormone production in human gastrointestinal carcinoid cells via a pathway dependent on MEK activation, Raf is regulated through phosphorylation and N terminus-C terminus interaction, a functional phosphatidate binding site is necessary for Raf-1 function in embryonic development, Raf-1 has a role in modulating integrin-stimulated ERK activation when bound to CAMKII, together, our data suggest that the synergistic activation of Raf-1 kinase in response to PMA and H(2)O(2) occurs via mechanisms that involve an interaction of Raf-1 kinase and PKC-epsilon., mutation analysis of the conserved regions in the RAF1 gene in human colorectal adenocarcinoma, Ovarian cancers demonstrate differential sensitivity to antisense oligonucleotides targeted against Raf-1, and target expression levels., Despite the effects of constitutively active Raf on pro-B cell expansion in Raf transgenic mice, Raf activation is not sufficient to rescue early B cell development in IL-7 receptor-deficient mice., RAF1 promotes herpesvirus 8 infection., Changes in flexibility upon protein-protein complex formation of H-Ras & the Ras-binding domain of C-Raf1 have been investigated using the molecular framework approach FIRST and molecular dynamics simulations of in total approximately 35 ns length., Raf1 kinase is released when it is hyperphosphorylated and activated during oxidative and other stresses, Raf1 and MAPK-activated protein kinase 2 are activated by L-ascorbic acid in acute myeloid leukemia cells., Raf1 potentiates drug-stimulated cyclic AMP accumulation in cells expressing adenyl cyclcase 6 after activation of multiple signaling pathways., Raf-1 links mitogenic signaling to Retinoblastoma Protein and that disruption of this interaction could aid in controlling proliferative disorders, findings indicate that ligation of retinol to a specific site embedded in the regulatory domain is an important feature of c-Raf regulation in the redox pathway., proteomic analysis of Raf-1 signaling complexes was used to show that Raf-1 counteracts apoptosis by suppressing the activation of mammalian sterile 20-like kinase (MST2), a novel Ras-independent ERK1/2 activation system in which p110gamma/Raf-1/MEK1/2 and PKA/B-Raf/MEK1/2 cooperate to activate ERK1/2., The induction of the raf-1/MEK1 pathway blocks IGF-1-mediated intracellular neuroendocrine hormone regulation. This pathway may be a therapeutic target in gastrointestinal carcinoid tumor therapy., Raf-1 may be involved in angiogenesis by controlling the expression of angiogenesis-related factors; study provides a possible strategy for the treatment of tumor angiogenesis by targeting Raf-1, the HER2/Raf-1/AP-1 axis may promote the development of androgen insensitive prostate cancer, leading to early relapse, Role for caspase-9 mediated cleavage of Raf-1 in the negative feedback regulation of hematopoietic cell apoptosis induced by growth factor withdrawal., regulated by an N-terminal autoinhibitory domain whose actions are blocked by interaction with Ras, essential role of Ras-induced conformational change in mitogen-activated protein kinase kinase activation by c-Raf, activation is regulated by CNK1, Pak1-dependent Raf-1 phosphorylation regulates its mitochondrial localization, phosphorylation of BAD, and Bcl-2 association, Raf-1 phosphorylation on serine 338 (S338) is a critical step in EGF aktivation of ERK that is lost in nonadherent cells., Raf-1 may mediate its anti-apoptotic function by interrupting ASK1-dependent phosphorylation of ALG-2., Activation of raf-1 leads to cessation of cell growth and suppression of calcitonin and chromogranin A production, results suggest that activated JNK can, in turn, activate not only jun but also raf that, in turn, activates MEK that can then cross-activate JNK in a positive feedback loop, selective reduction in catalytic activity and expression of B-Raf but not Raf-1 suggest that B-Raf may be playing an important role in altered ERK signaling in brain of suicide subjects, and thus in the pathophysiology of suicide, PP2A ABalphaC and ABdeltaC holoenzymes function as positive regulators of Raf1-MEK1/2-ERK1/2 signaling by targeting Raf1, Coll I activates the ERK/MAP Kinase pathway in Jurkat T cells through the activation of Ras and Raf-1., Erbin has a regulatory role in the Ras-Raf-MEK pathway and may inhibit ERK activation by disrupting the Sur-8-Ras/Raf interaction, data suggest that Raf-1 is the predominant Raf isoform responsible for regulating cellular growth in ovarian cancer cells and may be particularly important in high grade serous ovarian cancers, Data suggest that B-RAF activates C-RAF through a mechanism involving 14-3-3 mediated heterooligomerization and C-RAF transphosphorylation., inhibition of Raf-1 using an antisense raf oligonucleotide (AS-raf-ODN) to identify downstream targets of Raf-1 using microarray gene expression analysis, Merlin and MLK3 can interact in situ and merlin can disrupt the interactions between B-Raf and Raf-1 or those between MLK3 and either B-Raf or Raf-1., CD44 interaction with LARG and EGFR plays a pivotal role in Rho/Ras co-activation, PLC epsilon-Ca2+ signaling, and Raf/ERK up-regulation required for CaMKII-mediated cytoskeleton function and in head and neck squamous cell carcinoma progression, intracellular generation of NO* by nNOS leads to S-nitrosylation of H-Ras, which interferes with Raf-1 activation and propagation of signalling through ERK1/2, Rodent and human tumor cells containing constitutively activated Raf/Raf/MEK/ERK pathways were resistant to mda-5-induced killing., This work provides new insight into how the cell microenvironment may influence Raf-1 expression to modulate cell-Fibronectin interactions in 3D., Rheb has a central role in the regulation of the Ras/B-Raf/C-Raf/MEK signaling network, Nicotine induces cell proliferation by beta-arrestin-mediated activation of the Src and Rb-Raf-1 pathways om ;img camcer., These findings support the thesis that Raf-1 signals cell proliferation and cell differentiation through different intermediary proteins., findings identify MEK/ERK as a new signaling pathway activated by NPM/ALK and indicate that the pathway represents a novel therapeutic target in the ALK-induced malignancies, These findings support a role of Slug in mediating Raf 1-induced transcriptional repression of occludin and subsequent epithelial to mesenchymal transition., These studies identify XIAP as a new substrate of Raf-1., cAMP suppresses CRAF in melanocytes. This suppresses the oncogenic potential of CRAF. When RAS is mutated in melanoma, the cells switch their signaling from BRAF to CRAF, dysregulating cAMP signaling & allowing CRAF to signal to MEK., Based on these findings, we speculate that Raf-1 is activated to effectively mediate Ras-dependent signals in Alzheimer's disease., The Raf kinase inhibitory protein (RKIP) binds to Raf-1 interfering with binding of the MEK substrate and potentially also Raf-1 activation., Data suggest that Raf-1 may interfere with the role of Rad24 by competing with Rad24 for binding to Cdc25 or a direct phosphorylation of Cdc25, bypassing the checkpoint pathway in DNA repair through Cdc25 activation., in human airway smooth muscle cells, The interaction between eEF-1A and C-Raf increases eEF-1A stability and induces a survival activity., The results suggest that multiple cellular signaling pathways can reactivate the virus in a genetically homogeneous cell population. Further analysis revealed that the Raf/MEK/ERK/Ets-1 pathway mediates Ras-induced reactivation., Hepatitis B virus X protein stimulates the mitochondrial translocation of Raf-1 via oxidative stress, different pathogens (ie. Mycobacterium tuberculosis, M. leprae, Candida albicans, measles virus, and HIV-1) interacted with DC-SIGN to activate the Raf-1-acetylation-dependent signaling pathway to modulate signaling by different TLRs, results show overexpression of RAF-1 in mantle cell leukemia compared with tonsilar B-lymphocytes, Study identified 5 mutations in RAF1 in 10 individuals with Noonan syndrome; those with mutations causing changes in the CR2 domain of RAF1 had hypertrophic cardiomyopathy, while those with mutations leading to changes in the CR3 domain did not., Study reports that 18 of 231 individuals with Noonan syndrome and 2 of 6 individuals with LEOPARD syndrome without PTPN11 mutations have missense mutations in RAF1, which encodes a serine-threonine kinase that activates MEK1 and MEK2., Raf-1 may interfere with the role of Rad24 by competing with Rad24 for binding to Cdc25 in DNA repair, bypassing the checkpoint pathway through Cdc25 activation., In contrast to C-RAF that requires farnesylated H-Ras, cytosolic B-RAF associates effectively and with significantly higher affinity with both farnesylated and nonfarnesylated H-Ras., reveal a paradigm of spatial regulation of Raf kinase by RKTG via sequestrating Raf-1 to the Golgi apparatus and thereby inhibiting the ERK signaling pathway, A pathway comprising PKCs>Raf-1>MEK-1>ERK-1/-2 mediates the effect of gastrin on the CgA promoter, and strongly suggests that enhanced phosphorylation of Sp1 and CREB is crucial for CgA transactivation through the G protein-coupled CCK-B/gastrin receptor., activated Ras, Golgi apparatus-localized Lck is needed for the full activation of Raf-1, Raf-1 in beta-cells led to a striking loss of Bad phosphorylation at serine 112 and an increase in the protein levels of both Bad and Bax, GRP78 may stabilize Raf-1 to maintain mitochondrial permeability and thus protect cells from endoplasmic reticulum stress-induced apoptosis., These results suggest that 0.05 Gy of ionizing radiation stimulates cell proliferation through the transient activation of Raf and Akt in CCD-18 Lu cells., Loss-of-function RKIP mutants still appear to bind to Raf-1. However the stability of the complexes formed between mutants and the N-region Raf-1 phosphopeptide were drastically reduced., These results suggest that oncogenic ras-p21 induces phosphorylation of both raf-Ser259 and Ser338 and that raf-Ser 259 phosphorylation may be effected by activated JNK., C-RAF is the only isoform that directly binds mitochondria, PAK5 is a potent regulator of Raf-1 activity and may control Raf-1 dependent signaling at mitochondria, Increased Raf-1 kinase is associated with glioma formation, the Rb/Raf-1 interaction has a role in cell proliferation and angiogenesis, RAS signaling in colorectal carcinomas through alteration of RAS, RAF, NF1, and/or RASSF1a., AhR is a master regulator of c-raf and propose cross-talk between AhR and the mitogen-activated protein kinase signaling pathway., The state of activation of components of mTOR, Ras/Raf kinase/ERK, and nuclear factor (NF)-kappaB signal transduction pathways, as well as cell cycle protein analyte correlates in gastric adenocarcinoma cases, was examined., study identified a group of melanomas with low-activity BRAF mutations (G469E- and D594G) that are reliant upon CRAF-mediated survival activity, phosphatidate promotes ERK phosphorylation in intact cells but does not activate Raf in vitro, the molecular interactions of arrestin2 and arrestin3 and their individual domains with the components of the two MAPK cascades, ASK1-MKK4-JNK3 and c-Raf-1-MEK1-ERK2, These data show an unexpected role of XIAP and cellular-inhibitor of apoptosis proteins in the turnover of C-RAF protein, thereby modulating the MAPK signalling pathway and cell migration., Mutations in the RAF1 are associated with Noonan syndrome., RAF may induce cell proliferation through hypermethylation of tumor suppressor gene p16INK4A, Alpha-adducin and Raf-1 kinase are redistributed and localized to the inclusion membrane in Chlamydia and Chlamydophila infected cells., Vitamin D3-triggered differentiation of human myeloid leukemia cells depends on downregulation of Akt, which dissociates from Raf1 and activates MAPK signaling., dectin-1 activates two independent signaling pathways, one through Syk and one through Raf-1, to induce immune responses., Results identify a nuclear redistribution of Raf1 during the retinoic acid-induced differentiation of HL-60 cells., loss of RKIP is a functional somatic event in carriers of C-RAF germline mutations, which contributes to the development of t-AML, Oncogenic RAF1 rearrangement and a novel BRAF mutation as alternatives to KIAA1549, GILZ1 and SGK1 provide a physical and functional link between the PI3K- and Raf-1-dependent signaling modules, Targeting NRAS alone or both BRAF and CRAF in combination or both BRAF and PIK3CA together showed delay in tumor growth., Phosphorylation of S621 turns over rapidly and is enriched in the activated pool of endogenous Raf-1., Data show that sorafenib inhibited the raf/ MEK/ERK signal pathway, and downregulated cyclin D1 and Rb levels., Sorafenib inhibits NSCLC cell growth by targeting B-RAF in cells with wild-type KRAS and C-RAF in those with mutant KRAS., Data show that in the presence of negative feedback, changes in the rate of Ras-c-Raf binding have little effect on ERK activation., DGKeta acts as a novel critical regulatory component of the Ras/B-Raf/C-Raf/MEK/ERK signaling cascade via a previously unidentified mechanism., DC-SIGN was constitutively associated with a signalosome complex consisting of the scaffold proteins LSP1, KSR1 and CNK and the kinase Raf-1., The C-Raf expression is up-regulated in a subset of melanomas but not in nevi, suggesting that it might be a valuable diagnostic marker and therapeutic target., Studies provide models for Ras in association with Raf kinase, RalGDS and PI3Kalpha and PI3Kgamma., Data show that in hypoxic conditions or coexpressed with a constitutively active form of HIF-1alpha, c-Kit mutants activate the Ras/Raf/Mek/Erk pathway, stimulate proliferation and transform melanocytes., analysis of molecular pertubations allowing dysplasia to progress further to adenocarcinoma induced by exaggerted c-Raf kinase activity, Thus, the short hairpin-looped ODN-Raf, targeting the same region of c-raf-1 as miR-125b, is a multifunctional molecule reducing the expression of oncoproteins and stimulating cell death., Bcl-2-associated anthanogene 1 (BAG-1)'s effects were associated with an activation of RAF-1-a known binding partner of BAG-1, enhanced signaling through the MAP kinase pathway and a decrease in BIM expression., Data show that RAF not only neutralizes BAD's pro-apoptotic activity but activates it for a new function as a pore., Data show that melanoma cells expressing B-Raf(V600E) display a reduced C-Raf, Noonan syndrome (NS) is an autosomal dominant disorder caused by mutations in several proteins, including RAF1, which may later involve tumor onsets., dephosphorylation of S259 is the primary pathogenic mechanism in the activation of RAF1 mutants located in the CR2 domain as well as of downstream ERK, Results indicate that the Shoc2 scaffold protein modulates Ras-dependent Raf1 activation in a Ca(2+)- and calmodulin-dependent manner., Data show T117/T384 as Akt phosphorylation sites in MST2, and mutation of these sites inhibited MST2 binding to Raf-1 but enhanced binding to RASSF1A, accentuating downstream c-jun N-Terminal Kinase and p38 MAPK signaling and promoting apoptosis., Study demonstrates that human TAP-1 regulates signaling in vertebrate cells, acting at a previously uncharacterized step of the Ras pathway by inhibiting the ability of Raf to translocate to activated Ras at the cell membrane., Infection with Chlamydia trachomatis led to the Akt-dependent, increased phosphorylation (and inactivation) of Raf-1 at serine-259., Raf-1 was dominant in terms of promoting both cell cycle progression and preventing apoptosis when compared to Akt-1, Based on our results, it is possible that a subtle dysfunction (expression) of the RAF1 gene is involved in the development of the most common male reproductive tract disorder - unilateral or bilateral cryptorchidism, Leukotriene B(4) BLT receptor signaling regulates the level and stability of cyclooxygenase-2 (COX-2) mRNA through restricted activation of Ras/Raf/ERK/p42 AUF1 pathway, Results suggest that RAGE, NOX, and H-Ras/Raf-1 are implicated in the up-regulation of HSF1 or PAI-1 in vascular EC under diabetes-associated metabolic stress., Findings suggest that modulating the C-RAFSer(259)/14-3-3 protein-protein interaction with a stabilizing small molecule may yield a novel potential approach for treatment of diseases resulting from an overactive Ras-RAF-MAPK pathway., Reduction in Raf-1 kinase inhibitory protein expression in gallbladder carcinoma contributes to invasion and metastasis and is a significant prognostic marker in patients with gallbladder carcinoma., Raf-1 over-expression was an independent prognostic factor of poor survival in hepatocellular carcinoma., JNK1, Raf-1 and Livin may be involved in the carcinogenesis of sporadic colorectal tubular adenoma., Hepatitis B virus could up-regulate Raf1 expression by enhancing the activity of its promoter in a dose-dependent manner, and HBs and HBx may be involved in this process., EZH2 expression-mediated downregulation of DNA damage repair leads to accumulation of recurrent RAF1 gene amplification in breast tumor initiating cells (BTICs), which activates p-ERK-beta-catenin signaling to promote BTIC expansion., c-Raf plays a unique role in mediating K-Ras signaling in non-small cell lung carcinoma and makes it a suitable target for therapeutic intervention., Studies indicate that Raf kinases are excellent molecular targets for anticancer therapy., Downregulation of RKIP increased the level of free Raf-1 and thereby elevated the mitochondrial translocation of Raf-1 during HBx-mediated hepatocarcinogenesis., The H-Ras-ERK-induced and HO-1-mediated pathway could protect renal cancer cells from apoptosis., study demonstrates a novel role of the Raf/MEK/ERK pathway in regulating AR expression in certain PCa types and provides an insight into PCa responses to its aberrant activation, Report cooperative effects of Akt-1 and Raf-1 on the induction of cellular senescence in doxorubicin or tamoxifen treated breast cancer cells., Protein arginine methyltransferase 5 regulates ERK1/2 signal transduction amplitude and cell fate through CRAF., These results demonstrate that replicative and oxidative stresses are not required for RAF-induced senescence, and this senescence is readily reversed upon loss of cyclin-dependent kinases., CRAF is required for mitotic progression. Phospho-Ser338 CRAF is upregulated in mitosis and localizes to the mitotic spindles in human cell lines and tumor biopsies., ndings demonstrate that Pak1 phosphorylates BAD directly at S111, but phosphorylated S112 through Raf-1., High RAF1 is associated with hepatocellular carcinoma., Conditional expression of oncogenic C-RAF in mouse pulmonary epithelial cells reveals differential tumorigenesis and induction of autophagy leading to tumor regression., Ras/Raf-1/MEK/ERK signal pathway is important for chemokine ligand CCL2-induced migration activity and matrix metalloproteinase (MMP)-9 expression., Cellular Raf-1 levels determine endometrial stromal cell motility and morphology., Data show that bilirubin interacts with the Raf/ERK/MAPK pathway, effect on cyclin D1 and Raf content, altered retinoblastoma protein profile of hypophosphorylation, calcium influx, and YY1 proteolysis., Raf-1/JNK /p53/p21 pathway may be involved in apoptosis, and NFkappaB1 may play a possible role in inhibiting apoptosis., LEOPARD syndrome, both with proven mutations in the RAF1 gene not previouslyreported, Interleukin-6, osteopontin and Raf/MEK/ERK signaling modulate the sensitivity of human myeloma cells to alkylphosphocholines., amplification of Raf1, MEK/MAPK oncogenic signaling during tumor growth promotes the genesis of metastatic lesions from primary tumors by activating the mesenchymal epithelial transition., RKIP expression may serve as a novel clinical biomarker in patients with esophageal squamous cell carcinoma., PP242 mTOR inhibitor activates ERK in multiple myeloma cells via a target of rapamycin complex 1 (TORC1)/eukaryotic translation initiation factor 4E (eIF-4E)/RAF pathway and activation is a mechanism of resistance, The consequence of complex formation is a DiRas3-mediated recruitment and anchorage of C-RAF to components of the membrane skeleton, suppression of C-RAF/B-RAF heterodimerization, and inhibition of C-RAF kinase activity., unknown role for ML-IAP in controlling C-RAF stability and cell migration., These findings demonstrate that overexpression of Raf-1, p-Raf-1 or both could be considered as a new independent prognostic biomarker for poor survival rates for non-small cell lung cancer patients, Data indicate that erufosine caused dose-dependent decreases in the phosphorylation of PI3K (p85), Akt (PKB) at Thr 308 and cRaf in both MCF-7 and MDA-MB 231 cell lines., RAF1(D486N), as well as other kinase-impaired RAF1 mutants, showed increased heterodimerization with Braf, which was necessary and sufficient to promote increased MEK/ERK activation., Investigated BRAF and RAF1 alterations in Chinese prostate cancer.Found BRAF truncated in five of 200 informative Chinese cases & RAF1 was truncated in three of 204 informative cases and genomic rearrangements were correlated w/high Gleason scores., Gefitinib reverses the MDR protein gene expression and restores sensitivity of pancreatic cancer cells resistant to gemcitabine via RAF1/ERK signaling pathway., Determination of a 1, ARAF seems to stabilize BRAF, osteosarcoma patients whose tumors expressed raf-1 had a poorer clinical outcome than those whose tumors did not., SHOC2 and CRAF mediate ERK1/2 reactivation in mutant NRAS-mediated resistance to RAF inhibitor., results suggest a novel mechanism that the interaction of Raf-1 with cytoskeletal actin is critical for Raf-1 redistribution and airway smooth muscle cell proliferation during activation with the growth factor, The dominant effect of prolonged USP15 depletion upon signal amplitude is due to a decrease in CRAF levels while allowing for the possibility that USP15 may also function to dampen MAPK signaling through direct stabilization of BRAP., these findings establish RanBPM as a novel inhibitor of the ERK pathway through an interaction with the c-Raf complex and a regulation of c-Raf stability, DiRas3 interacts with C-RAF and downregulates MEK1 activity to restrict cell migration., Ras pathway activation via EGF treatment induced strong binding between B-Raf and C-Raf and a low level of binding between B-Raf and A-Raf., The ability of MEK to activate C-Raf was only partially dependent on MEK kinase activity but required MEK binding to C-Raf, suggesting that the binding results in a conformational change that increases C-Raf susceptibility to phosphorylation, Aberrant BRAF splice variants with deletions in both kinase and RAS-binding domains in rheumatoid arthritis patients demonstrate that these BRAF splice variants constitutively activate MAPK through CRAF, Antisense oligonucleotides targeting BCL-2 and C-RAF transcripts in tumor cell lines increases sensitivity to cytotoxic effect of etoposide., we identified multiple C-RAF mutations that produced biochemical and pharmacologic resistance in melanoma cell lines, Expression of miR-195 or knockdown of Raf-1 can similarly reduce tumor cell survival., activation of RAF1-MEK1-ERK/AKT axis may determine the resistance of non-small cell lung cancer cell lines bearing wild type EGFR to erlotinib, We hypothesize a potential direct or indirect role for SRC, RAF1, PTK2B genes in neurotransmission and in central nervous system signaling processes., 4 genes (EGFR, ERBB2, PTK2, and RAF1) with five SNPs (rs11238349, rs17172438, rs984654, rs11773818, and rs17172432) might be pivotal factors in the development of prostate cancer., Small G proteins Rac1 and Ras regulate serine/threonine protein phosphatase 5 (PP5).extracellular signal-regulated kinase (ERK) complexes involved in the feedback regulation of Raf1., The higher expression of RAF1 mRNA and the activation of AKT/ERK proteins in vinorelbine-resistant non-small cell lung cancer cell lines may confer resistance to vinorelbine, A novel mechanism for response was discovered whereby high expression level of CAV-1 at the plasma membrane disrupts the BRaf/CRaf heterodimer and thus inhibits the activation of MAPK pathway during dasatinib treatment., analysis of RAF1 mutations in cohorts of South Indian, North Indian and Japanese patients with childhood-onset dilated cardiomyopathy, Authors demonstrate that the N-terminus of human Raf1 kinase (hRaf11-147aa) binds with human RKIP (hRKIP) at its ligand-binding pocket, loop "127-149", and the C-terminal helix by nuclear magnetic resonance experiments., Including several anti-apoptotic Bcl-2 family members and c-Raf., Results show that ubiquitination and levels of RAF-1 is controlled by both Shoc2 and HUWE1., These data suggest that miR-7-5p functions as a tumor suppressor gene to regulate glioblastoma microvascular endothelial cell proliferation potentially by targeting the RAF1 oncogene, Studied the promoter methylation and RNA expression profiles of ERK and RAF1 genes with risk of oral squamous cell carcinoma (OSCC) along with the promoter methylation status of ERK and RAF1 genes., our study demonstrated that miR-455-RAF1 may represent a new potential therapeutic target for colorectal carcinoma treatment., truncated RAF1 and BRAF proteins, recently described as products of genomic rearrangements in gastric cancer and other malignancies, have the ability to render neoplastic cells resistant to RTK-targeted therapy, approach identified 18 kinase and kinase-related genes whose overexpression can substitute for EGFR in EGFR-dependent PC9 cells, and these genes include seven of nine Src family kinase genes, FGFR1, FGFR2, ITK, NTRK1, NTRK2, MOS, MST1R, and RAF1., Aberrant expression of A-, B-, and C-RAF, and COT is frequent in PTC; increased expression of COT is correlated with recurrence of PTC., In the presence of Raf1, the RasQ61L mutant has a rigid switch II relative to the wild-type and increased flexibility at the interface with switch I, which propagates across Raf-Ras binding domain., Abnormal activation of the Ras/MAPK pathway may play a significant role in the development of pulmonary vascular disease in the subset of patients with Noonan syndrome and a specific RAF1 mutation., Data indicate that cyclic AMP signaling reduces the expression of sirtuin 6 deacetylase via inhibition of the c-Raf-MEK1-ERK1/2 pathway., Raf-1 may be an important biomarker in predicting the prognosis of chordoma patients., Suggest an interrelated kinase module involving c-Raf/PI3K/Lyn and perhaps Fgr functions in a nontraditional way during retinoic acid-induced maturation or during rescue of RA induction therapy using inhibitor co-treatment in RA-resistant leukemia cells., a model that CD166 regulates MCAM through a signaling flow from activation of PI3K/AKT and c-Raf/MEK/ERK signaling to the inhibition of potential MCAM ubiquitin E3 ligases, betaTrCP and Smurf1., DJ-1 directly binds to the kinase domain of c-Raf to stimulate its self-phosphorylation, followed by phosphorylation of MEK and ERK1/2 in EGF-treated cells., Besides mediating the anticancer effect, pDAPK(S308) may serve as a predictive biomarker for Raf inhibitors combination therapy, suggesting an ideal preclinical model that is worthy of clinical translation., This study provides the molecular basis for C-Raf C-terminal-derived phosphopeptide interaction with 14-3-3zeta protein and gives structural insights responsible for phosphorylation-mediated protein binding., Up-regulation of Raf-1 is associated with triple-negative breast cancer., our study suggested that black rice anthocyanins extract suppress metastasis in breast cancer cells by targeting the RAS/RAF/MAPK pathway, c-Raf interacts with MEK1 and activates MEK1 by phosphorylation.,
OMIM_DISEASE Noonan syndrome 5, LEOPARD syndrome 2, Cardiomyopathy, dilated, 1NN,
SP_COMMENT catalytic activity:ATP + a protein = ADP + a phosphoprotein., cofactor:Binds 2 zinc ions per subunit., disease:Defects in RAF1 are the cause of LEOPARD syndrome type 2 (LEOPARD syndrome-2) [MIM:611554]. LEOPARD syndrome is an autosomal dominant disorder allelic with Noonan syndrome. The acronym LEOPARD stands for lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormalities of genitalia, retardation of growth, and deafness., disease:Defects in RAF1 are the cause of Noonan syndrome type 5 (NS5) [MIM:611553]. Noonan syndrome (NS) is a disorder characterized by dysmorphic facial features, short stature, hypertelorism, cardiac anomalies, deafness, motor delay, and a bleeding diathesis. It is a genetically heterogeneous and relatively common syndrome, with an estimated incidence of 1 in 1000-2500 live births., function:Involved in the transduction of mitogenic signals from the cell membrane to the nucleus. Part of the Ras-dependent signaling pathway from receptors to the nucleus. Protects cells from apoptosis mediated by STK3., PTM:Phosphorylated upon DNA damage, probably by ATM or ATR. Phosphorylation at Thr-269 increases its kinase activity., similarity:Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. RAF subfamily., similarity:Contains 1 phorbol-ester/DAG-type zinc finger., similarity:Contains 1 protein kinase domain., similarity:Contains 1 RBD (Ras-binding) domain., subunit:Interacts with Ras proteins; the interaction is antagonized by RIN1. Weakly interacts with RIT1 (By similarity). Interacts with STK3; the interaction inhibits its pro-apoptotic activity. Interacts with YWHAZ (unphosphorylated at 'Thr-232')., tissue specificity:In skeletal muscle, isoform 1 is more abundant than isoform 2.,