Gene Symbol: Braf
Description: B-Raf proto-oncogene, serine/threonine kinase
Alias: serine/threonine-protein kinase B-raf, v-raf murine sarcoma viral oncogene homolog B, v-raf murine sarcoma viral oncogene homolog B1
Species: rat
Products:     Braf

Top Publications

  1. Camarero G, Tyrsin O, Xiang C, Pfeiffer V, Pleiser S, Wiese S, et al. Cortical migration defects in mice expressing A-RAF from the B-RAF locus. Mol Cell Biol. 2006;26:7103-15 pubmed
    ..Our data reveal that B-RAF is an important mediator of neuronal survival, migration, and dendrite formation and that A-RAF cannot fully compensate for these functions. ..
  2. Niihori T, Aoki Y, Narumi Y, Neri G, Cave H, Verloes A, et al. Germline KRAS and BRAF mutations in cardio-facio-cutaneous syndrome. Nat Genet. 2006;38:294-6 pubmed
    ..In 43 individuals with CFC, we identified two heterozygous KRAS mutations in three individuals and eight BRAF mutations in 16 individuals, suggesting that dysregulation of the RAS-RAF-ERK pathway is a common molecular basis ..
  3. Chen A, Ohno M, Giese K, Kühn R, Chen R, Silva A. Forebrain-specific knockout of B-raf kinase leads to deficits in hippocampal long-term potentiation, learning, and memory. J Neurosci Res. 2006;83:28-38 pubmed
    ..Our findings demonstrate that B-raf plays a role in hippocampal ERK activation, synaptic plasticity, and L&M. ..
  4. Newbern J, Zhong J, Wickramasinghe R, Li X, Wu Y, Samuels I, et al. Mouse and human phenotypes indicate a critical conserved role for ERK2 signaling in neural crest development. Proc Natl Acad Sci U S A. 2008;105:17115-20 pubmed publisher
    ..2 micro-deletion are explained by deficiencies in neural crest autonomous ERK2 signaling. ..
  5. Palmedo G, Hantschke M, Rutten A, Mentzel T, Hugel H, Flaig M, et al. The T1796A mutation of the BRAF gene is absent in Spitz nevi. J Cutan Pathol. 2004;31:266-70 pubmed
    b>BRAF, a serine/threonine kinase, is a component of the retrovirus-associated sequence (RAS)-RAF-extracellular-regulated protein kinase (ERK)-MAP kinase signal transduction pathway mediating signals from RAS to ERK...
  6. Pakladok T, Hosseinzadeh Z, Alesutan I, Lang F. Stimulation of the Na(+)-coupled glucose transporter SGLT1 by B-RAF. Biochem Biophys Res Commun. 2012;427:689-93 pubmed publisher
    ..In conclusion, B-RAF upregulates SGLT1 activity, an effect requiring vesicle insertion into the cell membrane. ..
  7. Haling J, Sudhamsu J, Yen I, Sideris S, Sandoval W, Phung W, et al. Structure of the BRAF-MEK complex reveals a kinase activity independent role for BRAF in MAPK signaling. Cancer Cell. 2014;26:402-413 pubmed publisher
    Numerous oncogenic mutations occur within the BRAF kinase domain (BRAF(KD)). Here we show that stable BRAF-MEK1 complexes are enriched in BRAF(WT) and KRAS mutant (MT) cells but not in BRAF(MT) cells...
  8. Valluet A, Druillennec S, Barbotin C, Dorard C, Monsoro Burq A, Larcher M, et al. B-Raf and C-Raf are required for melanocyte stem cell self-maintenance. Cell Rep. 2012;2:774-80 pubmed publisher
    ..Therefore, Raf signaling is dispensable for early melanocyte lineage development, but necessary for MSC maintenance. ..
  9. Wojnowski L, Stancato L, Larner A, Rapp U, Zimmer A. Overlapping and specific functions of Braf and Craf-1 proto-oncogenes during mouse embryogenesis. Mech Dev. 2000;91:97-104 pubmed
    ..Here we describe the phenotype of mouse mutants with different combinations of mutant Craf-1 and Braf alleles...

More Information


  1. Pritchard C, Hayes L, Wojnowski L, Zimmer A, Marais R, Norman J. B-Raf acts via the ROCKII/LIMK/cofilin pathway to maintain actin stress fibers in fibroblasts. Mol Cell Biol. 2004;24:5937-52 pubmed
    Recent data have shown that the BRAF gene is mutated at a high frequency in human malignancies...
  2. Kelly P, Rahmani Z. DYRK1A enhances the mitogen-activated protein kinase cascade in PC12 cells by forming a complex with Ras, B-Raf, and MEK1. Mol Biol Cell. 2005;16:3562-73 pubmed
  3. James J, Ruggeri B, Armstrong R, Rowbottom M, Jones Bolin S, Gunawardane R, et al. CEP-32496: a novel orally active BRAF(V600E) inhibitor with selective cellular and in vivo antitumor activity. Mol Cancer Ther. 2012;11:930-41 pubmed publisher
    Mutations in the BRAF gene have been identified in approximately 7% of cancers, including 60% to 70% of melanomas, 29% to 83% of papillary thyroid carcinomas, 4% to 16% colorectal cancers, and a lesser extent in serous ovarian and non-..
  4. Honecker F, Wermann H, Mayer F, Gillis A, Stoop H, van Gurp R, et al. Microsatellite instability, mismatch repair deficiency, and BRAF mutation in treatment-resistant germ cell tumors. J Clin Oncol. 2009;27:2129-36 pubmed publisher
    ..b>BRAF mutation (V600E) is found in MSI colorectal cancers...
  5. Willard M, Willard F, Li X, Cappell S, Snider W, Siderovski D. Selective role for RGS12 as a Ras/Raf/MEK scaffold in nerve growth factor-mediated differentiation. EMBO J. 2007;26:2029-40 pubmed
    ..These data suggest that RGS12 may play a critical, and receptor-selective, role in coordinating Ras-dependent signals that are required for promoting and/or maintaining neuronal differentiation. ..
  6. Verbruggen M, Sieben N, Roemen G, Rockx D, van Diest P, Verheijen R, et al. v-Raf murine sarcoma viral oncogene mutation status in serous borderline ovarian tumors and the effect on clinical behavior. Int J Gynecol Cancer. 2009;19:1560-3 pubmed publisher
    To determine the incidence of activating v-raf murine sarcoma viral oncogene (BRAF) mutations in 30 serous borderline tumors (SBTs) of the ovary and the accompanying implants and to link BRAF mutation status to the clinical behavior of ..
  7. Russo A, Borger D, Szymonifka J, Ryan D, Wo J, Blaszkowsky L, et al. Mutational analysis and clinical correlation of metastatic colorectal cancer. Cancer. 2014;120:1482-90 pubmed publisher
    ..001) and with age ?56 years (7% vs 0.9%; P = .02). Conversely, v-raf murine sarcoma viral oncogene homolog B (BRAF) mutations were associated with colon cancer (13% vs 3%; P =?.024) and older age (15.8% vs 4.6%; P = .006)...
  8. Valluet A, Hmitou I, Davis S, Druillennec S, Larcher M, Laroche S, et al. B-raf alternative splicing is dispensable for development but required for learning and memory associated with the hippocampus in the adult mouse. PLoS ONE. 2010;5:e15272 pubmed publisher
    ..In contrast, mice mutated on exon 8b are not impaired in this function. Interestingly, our results suggest that exon 8b is present only in eutherians and its splicing is differentially regulated among species...
  9. Tsukamoto H, Irie A, Senju S, Hatzopoulos A, Wojnowski L, Nishimura Y. B-Raf-mediated signaling pathway regulates T cell development. Eur J Immunol. 2008;38:518-27 pubmed publisher
    ..In conclusion, we present first evidence for the important role of B-Raf-mediated signaling in T cell development. ..
  10. Preto A, Figueiredo J, Velho S, Ribeiro A, Soares P, Oliveira C, et al. BRAF provides proliferation and survival signals in MSI colorectal carcinoma cells displaying BRAF(V600E) but not KRAS mutations. J Pathol. 2008;214:320-7 pubmed
    b>BRAF kinase is a downstream target of KRAS and activates the MAPK pathway...
  11. Andreadi C, Cheung L, Giblett S, Patel B, Jin H, Mercer K, et al. The intermediate-activity (L597V)BRAF mutant acts as an epistatic modifier of oncogenic RAS by enhancing signaling through the RAF/MEK/ERK pathway. Genes Dev. 2012;26:1945-58 pubmed publisher
    L597V)BRAF mutations are acquired somatically in human cancer samples and are frequently coincident with RAS mutations...
  12. Walentinsson A, Helou K, Wallenius V, Hedrich H, Szpirer C, Levan G. Independent amplification of two gene clusters on chromosome 4 in rat endometrial cancer: identification and molecular characterization. Cancer Res. 2001;61:8263-73 pubmed
    ..Taken together, our findings suggest that up-regulation of Cdk6 and/or Met may contribute to the development of endometrial cancers in the BDII rat. ..
  13. Couto J, Daly L, Almeida A, Knauf J, Fagin J, Sobrinho Simoes M, et al. STAT3 negatively regulates thyroid tumorigenesis. Proc Natl Acad Sci U S A. 2012;109:E2361-70 pubmed publisher
    ..cell lines [harboring rearranged during transfection (RET)/PTC, v-RAF murine sarcoma viral oncogene homolog B (BRAF), or rat sarcoma virus oncogene (RAS) alterations], we determined that IL-6/gp130/JAK signaling is responsible for ..
  14. Hoeflich K, Gray D, Eby M, Tien J, Wong L, Bower J, et al. Oncogenic BRAF is required for tumor growth and maintenance in melanoma models. Cancer Res. 2006;66:999-1006 pubmed
    ..have developed inducible short-hairpin RNA xenograft models to examine the in vivo efficacy of inhibiting oncogenic BRAF. Our results show that tumor regression resulting from BRAF suppression is inducible, reversible, and tightly ..
  15. Nucera C, Nehs M, Nagarkatti S, Sadow P, Mekel M, Fischer A, et al. Targeting BRAFV600E with PLX4720 displays potent antimigratory and anti-invasive activity in preclinical models of human thyroid cancer. Oncologist. 2011;16:296-309 pubmed publisher
    ..PLX4720 was effective in reducing cell proliferation, migration, and invasion in this heterozygous model. PLX4720 therapy should be tested and considered for a phase I study for the treatment of patients with B-Raf(V600E) ATC. ..
  16. Sanders H, Albitar M. Somatic mutations of signaling genes in non-small-cell lung cancer. Cancer Genet Cytogenet. 2010;203:7-15 pubmed publisher
  17. Appleman V, Ahronian L, Cai J, Klimstra D, Lewis B. KRAS(G12D)- and BRAF(V600E)-induced transformation of murine pancreatic epithelial cells requires MEK/ERK-stimulated IGF1R signaling. Mol Cancer Res. 2012;10:1228-39 pubmed
    ..Here, we show that KRAS(G12D) and BRAF(V600E) enhance PDEC proliferation and increase survival after exposure to apoptotic stimuli in a manner dependent ..
  18. Dillon T, Takahashi M, Li Y, Tavisala S, Murray S, Moran A, et al. B-Raf is required for positive selection and survival of DP cells, but not for negative selection of SP cells. Int Immunol. 2013;25:259-69 pubmed publisher
    ..Surprisingly, we saw no effect of B-Raf deficiency on negative selection of autoreactive SP thymocytes, despite the greatly reduced ERK activation in these cells. ..
  19. Collisson E, Trejo C, Silva J, Gu S, Korkola J, Heiser L, et al. A central role for RAF?MEK?ERK signaling in the genesis of pancreatic ductal adenocarcinoma. Cancer Discov. 2012;2:685-93 pubmed
    ..Here, we show that expression of BRAF(V600E), but not PIK3CA(H1047R), in the mouse pancreas leads to pancreatic intraepithelial neoplasia (PanIN) lesions...
  20. Subramanian J, Dye L, Morozov A. Rap1 signaling prevents L-type calcium channel-dependent neurotransmitter release. J Neurosci. 2013;33:7245-52 pubmed publisher
    ..We propose that the Rap1 signaling enables plasticity and fear learning by regulating LTCCs at cortico-amygdala synapses. ..
  21. Pracht M, Mogha A, Lespagnol A, Fautrel A, Mouchet N, Le Gall F, et al. Prognostic and predictive values of oncogenic BRAF, NRAS, c-KIT and MITF in cutaneous and mucous melanoma. J Eur Acad Dermatol Venereol. 2015;29:1530-8 pubmed publisher
    Mutations of BRAF, NRAS and c-KIT oncogenes are preferentially described in certain histological subtypes of melanoma and linked to specific histopathological features...
  22. Kramann N, Hasenfuß G, Seidler T. B-RAF and its novel negative regulator reticulocalbin 1 (RCN1) modulates cardiomyocyte hypertrophy. Cardiovasc Res. 2014;102:88-96 pubmed publisher
    ..Our results show that B-RAF kinase activity is essential for cardiac hypertrophy and RCN1, its newly identified negative regulator, abolishes hypertrophic response of cardiomyocytes in vitro. ..
  23. Chen H, Wang L, D Mello S. Inhibition of ATF-3 expression by B-Raf mediates the neuroprotective action of GW5074. J Neurochem. 2008;105:1300-12 pubmed publisher
    ..Taken together our results indicate that all four indolones mediate neuroprotection by a common mechanism which involves B-Raf activation, and that a downstream target of B-Raf is ATF-3. ..
  24. Feng Y, Shiozawa T, Miyamoto T, Kashima H, Kurai M, Suzuki A, et al. BRAF mutation in endometrial carcinoma and hyperplasia: correlation with KRAS and p53 mutations and mismatch repair protein expression. Clin Cancer Res. 2005;11:6133-8 pubmed
    ..Recent studies have revealed frequent activating mutations of the gene for BRAF, an effector of Ras protein in the mitogen-activated protein kinase pathway, in several malignancies...
  25. Salgado C, Basu D, Nikiforova M, Bauer B, Johnson D, Rundell V, et al. BRAF mutations are also associated with neurocutaneous melanocytosis and large/giant congenital melanocytic nevi. Pediatr Dev Pathol. 2015;18:1-9 pubmed publisher
    NRAS and BRAF mutations occur in congenital melanocytic nevi (CMN), but results are contradictory. Sixty-six prospectively collected CMN patients were analyzed for NRAS Q61 mutations using Sanger sequencing...
  26. Thevakumaran N, Lavoie H, Critton D, Tebben A, Marinier A, Sicheri F, et al. Crystal structure of a BRAF kinase domain monomer explains basis for allosteric regulation. Nat Struct Mol Biol. 2015;22:37-43 pubmed publisher
    ..Atomic details of the monomer 'off' state have been elusive. Reinspection of the BRAF kinase domain structures revealed that sulfonamide inhibitors induce features of an off state, primarily a ..
  27. Roskoski R. MEK1/2 dual-specificity protein kinases: structure and regulation. Biochem Biophys Res Commun. 2012;417:5-10 pubmed publisher
    ..MEK1 regulation is unusual in that S212 phosphorylation in its activation segment is inhibitory. Moreover, active ERK catalyzes a feedback inhibitory phosphorylation of MEK1 T292 that serves to downregulate the pathway. ..
  28. Lee D, Cho Y, Kang S, Yoon N, Sung C, Suh Y. BRAF V600E mutations are frequent in dysembryoplastic neuroepithelial tumors and subependymal giant cell astrocytomas. J Surg Oncol. 2015;111:359-64 pubmed publisher
    b>BRAF mutation has received a great deal of attention in neuro-oncology field, recently. This study aimed to investigate the incidence and the clinical significance of BRAF(V600E) in low-grade glial tumors...
  29. Oh Y, Yue P, Zhou W, Balko J, Black E, Owonikoko T, et al. Oncogenic Ras and B-Raf proteins positively regulate death receptor 5 expression through co-activation of ERK and JNK signaling. J Biol Chem. 2012;287:257-67 pubmed publisher
  30. Trakul N, Menard R, Schade G, Qian Z, Rosner M. Raf kinase inhibitory protein regulates Raf-1 but not B-Raf kinase activation. J Biol Chem. 2005;280:24931-40 pubmed
    ..These results indicate that selective modulation of c-Raf-1 but not B-Raf activation by RKIP can limit the dynamic range of the MAPK signaling response to growth factors and may play a critical role in growth and development. ..
  31. Kimmelman A, Nuñez Rodriguez N, Chan A. R-Ras3/M-Ras induces neuronal differentiation of PC12 cells through cell-type-specific activation of the mitogen-activated protein kinase cascade. Mol Cell Biol. 2002;22:5946-61 pubmed
    ..Thus, R-Ras3 is implicated in a novel pathway of neuronal differentiation by coupling specific trophic factors to the MAPK cascade through the activation of B-Raf. ..
  32. Morice C, Nothias F, Konig S, Vernier P, Baccarini M, Vincent J, et al. Raf-1 and B-Raf proteins have similar regional distributions but differential subcellular localization in adult rat brain. Eur J Neurosci. 1999;11:1995-2006 pubmed
    ..Altogether these results suggest that each Raf protein could have a distinct signalling regulatory function in the brain with regard to its subcellular localization. ..
  33. Jeong J, Wang Z, Guimaraes A, Ouyang X, Figueiredo J, Ding Z, et al. BRAF activation initiates but does not maintain invasive prostate adenocarcinoma. PLoS ONE. 2008;3:e3949 pubmed publisher
    ..a genetically-engineered mouse (GEM) model of invasive prostate cancers, whereby an activating mutation of BRAF(V600E)--a mutation found in approximately 10% of human prostate tumors--was targeted to the epithelial compartment ..
  34. Ren J, Li Z, Sacks D. IQGAP1 modulates activation of B-Raf. Proc Natl Acad Sci U S A. 2007;104:10465-9 pubmed
    ..Our data identify a previously unrecognized interaction between IQGAP1 and B-Raf and suggest that IQGAP1 is a scaffold necessary for activation of B-Raf by EGF. ..
  35. Hong S, Jin D, Shin J, Moon J, Na Y, Jung K, et al. Ring finger protein 149 is an E3 ubiquitin ligase active on wild-type v-Raf murine sarcoma viral oncogene homolog B1 (BRAF). J Biol Chem. 2012;287:24017-25 pubmed publisher
    Members of the RAF family (ARAF, BRAF, and CRAF/RAF-1) are involved in a variety of cellular activities, including growth, survival, differentiation, and transformation...
  36. Packer L, Rana S, Hayward R, O Hare T, Eide C, Rebocho A, et al. Nilotinib and MEK inhibitors induce synthetic lethality through paradoxical activation of RAF in drug-resistant chronic myeloid leukemia. Cancer Cell. 2011;20:715-27 pubmed publisher
    ..and dasatinib possess weak off-target activity against RAF and, therefore, drive paradoxical activation of BRAF and CRAF in a RAS-dependent manner...
  37. Vuchak L, Tsygankova O, Prendergast G, Meinkoth J. Protein kinase A and B-Raf mediate extracellular signal-regulated kinase activation by thyrotropin. Mol Pharmacol. 2009;76:1123-9 pubmed publisher
    ..These data provide the first evidence for a functional role for B-Raf in TSH signaling. ..
  38. Xie Y, Wang Y, Sun T, Wang F, Trostinskaia A, Puscheck E, et al. Six post-implantation lethal knockouts of genes for lipophilic MAPK pathway proteins are expressed in preimplantation mouse embryos and trophoblast stem cells. Mol Reprod Dev. 2005;71:1-11 pubmed
    ..Studies on RNA expression using RT-PCR suggest that maternal RNA could play an important role in delaying the presence of the lethal phenotype of null mutations. ..
  39. Polzien L, Baljuls A, Rennefahrt U, Fischer A, Schmitz W, Zahedi R, et al. Identification of novel in vivo phosphorylation sites of the human proapoptotic protein BAD: pore-forming activity of BAD is regulated by phosphorylation. J Biol Chem. 2009;284:28004-20 pubmed publisher
    ..This pore-forming capacity was dependent on phosphorylation status and interaction with 14-3-3 proteins. Collectively, our findings provide new insights into the regulation of BAD function by phosphorylation. ..
  40. Park S, Yeung M, Beach S, Shields J, Yeung K. RKIP downregulates B-Raf kinase activity in melanoma cancer cells. Oncogene. 2005;24:3535-40 pubmed
    ..The low expression of RKIP and its antagonistic action on B-Raf suggests that RKIP may play an important role in melanoma turmorgenesis. ..
  41. Götz R, Wiese S, Takayama S, Camarero G, Rossoll W, Schweizer U, et al. Bag1 is essential for differentiation and survival of hematopoietic and neuronal cells. Nat Neurosci. 2005;8:1169-78 pubmed
    ..Our data show that Bag1 is a physiological mediator of extracellular survival signals linked to the cellular mechanisms that prevent apoptosis in hematopoietic and neuronal progenitor cells. ..
  42. Shi G, Han J, Andres D. Rin GTPase couples nerve growth factor signaling to p38 and b-Raf/ERK pathways to promote neuronal differentiation. J Biol Chem. 2005;280:37599-609 pubmed
  43. Kalmes A, Hagemann C, Weber C, Wixler L, Schuster T, Rapp U. Interaction between the protein kinase B-Raf and the alpha-subunit of the 11S proteasome regulator. Cancer Res. 1998;58:2986-90 pubmed
    ..No association could be found between PA28alpha and A-Raf or c-Raf-1. B-Raf binds to a region in PA28alpha that is important for its proteasome-activating function. ..
  44. Inoue S, Moriya M, Watanabe Y, Miyagawa Tomita S, Niihori T, Oba D, et al. New BRAF knockin mice provide a pathogenetic mechanism of developmental defects and a therapeutic approach in cardio-facio-cutaneous syndrome. Hum Mol Genet. 2014;23:6553-66 pubmed publisher
    ..Germline mutations in BRAF cause CFC syndrome, which is characterized by heart defects, distinctive facial features and ectodermal ..
  45. Cohen J, Labenski M, Mastrandrea N, Canatsey R, Monks T, Lau S. Transcriptional and post-translational modifications of B-Raf in quinol-thioether induced tuberous sclerosis renal cell carcinoma. Mol Carcinog. 2016;55:1243-50 pubmed publisher
    ..Transcriptional and post-translational characterization of critical kinases, such as B-Raf, may contribute to the progression of tuberous sclerosis RCC. (246/250) © 2015 Wiley Periodicals, Inc. ..
  46. Berruti G. A novel rap1/B-Raf/14-3-3 theta protein complex is formed in vivo during the morphogenetic differentiation of postmeiotic male germ cells. Exp Cell Res. 2000;257:172-9 pubmed
  47. Yu J, Deshmukh H, Gutmann R, Emnett R, Rodriguez F, Watson M, et al. Alterations of BRAF and HIPK2 loci predominate in sporadic pilocytic astrocytoma. Neurology. 2009;73:1526-31 pubmed publisher
    Independent studies have previously demonstrated that both the HIPK2 and BRAF genes are amplified and rearranged, respectively, in pilocytic astrocytomas (PAs)...
  48. Hagemann C, Patel R, Blank J. MEKK3 interacts with the PA28 gamma regulatory subunit of the proteasome. Biochem J. 2003;373:71-9 pubmed
    ..MEKK3 represents the first protein kinase capable of binding and phosphorylating a PA, and provides a potential mechanism to link stress-activated protein kinase signalling with the PA28 gamma-dependent proteasome. ..
  49. Kamata T, Kang J, Lee T, Wojnowski L, Pritchard C, Leavitt A. A critical function for B-Raf at multiple stages of myelopoiesis. Blood. 2005;106:833-40 pubmed
    ..Together, these data suggest that B-Raf plays a cell-autonomous role in megakaryocytopoiesis and a permissive role in myeloid progenitor development. ..
  50. Mesa C, Mirza M, Mitsutake N, Sartor M, Medvedovic M, Tomlinson C, et al. Conditional activation of RET/PTC3 and BRAFV600E in thyroid cells is associated with gene expression profiles that predict a preferential role of BRAF in extracellular matrix remodeling. Cancer Res. 2006;66:6521-9 pubmed
    ..e., the TK receptors RET or NTRK and the signaling proteins RAS and BRAF)...
  51. Wang Q, Satomi K, Oh J, Hutter B, Brors B, Diessl N, et al. Braf Mutations Initiate the Development of Rat Gliomas Induced by Postnatal Exposure to N-Ethyl-N-Nitrosourea. Am J Pathol. 2016;186:2569-76 pubmed publisher
    ..T->A mutations were identified in all five rat gliomas at Braf codon 545 (V545E), which corresponds to the human BRAF V600E...
  52. Gruppuso P, Boylan J. Hepatic epidermal growth factor-regulated mitogen-activated protein kinase kinase kinase activity in the rat: lack of identity with known forms of raf and MEKK. FEBS Lett. 2000;466:200-4 pubmed
    ..Our results indicate that hepatic, EGF-sensitive MEK kinase activity may reside with a previously unidentified and physiologically relevant form of Raf and/or MEKK. ..
  53. Rajakulendran T, Sahmi M, Lefrancois M, Sicheri F, Therrien M. A dimerization-dependent mechanism drives RAF catalytic activation. Nature. 2009;461:542-5 pubmed publisher
    ..Of note, one member of the RAF family, BRAF, is the most frequently mutated oncogene in the kinase superfamily...
  54. Estep A, Palmer C, McCormick F, Rauen K. Mutation analysis of BRAF, MEK1 and MEK2 in 15 ovarian cancer cell lines: implications for therapy. PLoS ONE. 2007;2:e1279 pubmed vitro experiments, were screened for mutations using bidirectional direct sequencing in all coding regions of BRAF, MEK1 and MEK2. BRAF mutations were identified in four of the fifteen ovarian cancer cell lines studied...
  55. Rushworth L, Hindley A, O Neill E, Kolch W. Regulation and role of Raf-1/B-Raf heterodimerization. Mol Cell Biol. 2006;26:2262-72 pubmed
  56. Terai K, Matsuda M. The amino-terminal B-Raf-specific region mediates calcium-dependent homo- and hetero-dimerization of Raf. EMBO J. 2006;25:3556-64 pubmed
    ..Thus, we propose that the hitherto unidentified function of the B-Raf amino-terminal region is to mediate calcium-dependent activation of B-Raf and the following MEK activation, which may occur in the absence of Ras activation. ..
  57. McCubrey J, Steelman L, Chappell W, Abrams S, Wong E, Chang F, et al. Roles of the Raf/MEK/ERK pathway in cell growth, malignant transformation and drug resistance. Biochim Biophys Acta. 2007;1773:1263-84 pubmed
  58. Karbowniczek M, Cash T, Cheung M, Robertson G, Astrinidis A, Henske E. Regulation of B-Raf kinase activity by tuberin and Rheb is mammalian target of rapamycin (mTOR)-independent. J Biol Chem. 2004;279:29930-7 pubmed
    ..Taken together these data demonstrate that inhibition of B-Raf kinase via Rheb is an mTOR-independent function of tuberin. ..
  59. Ren J, Li Z, Sacks D. IQGAP1 integrates Ca2+/calmodulin and B-Raf signaling. J Biol Chem. 2008;283:22972-82 pubmed publisher
    ..Collectively, our data identify a previously unrecognized mechanism in which the scaffold protein IQGAP1 couples Ca(2+) and calmodulin signaling to B-Raf function. ..
  60. Urosevic J, Sauzeau V, Soto Montenegro M, Reig S, Desco M, Wright E, et al. Constitutive activation of B-Raf in the mouse germ line provides a model for human cardio-facio-cutaneous syndrome. Proc Natl Acad Sci U S A. 2011;108:5015-20 pubmed publisher
    ..Moreover, they may serve as a tool to evaluate the potential therapeutic efficacy of B-RAF inhibitors and establish the precise window at which they could be effective against this congenital syndrome...
  61. Roring M, Herr R, Fiala G, Heilmann K, Braun S, Eisenhardt A, et al. Distinct requirement for an intact dimer interface in wild-type, V600E and kinase-dead B-Raf signalling. EMBO J. 2012;31:2629-47 pubmed publisher
    ..Our data further implicate the Raf DIF as a potential target against Ras-driven Raf-mediated (paradoxical) ERK activation. ..
  62. Santos S, Verveer P, Bastiaens P. Growth factor-induced MAPK network topology shapes Erk response determining PC-12 cell fate. Nat Cell Biol. 2007;9:324-30 pubmed
    ..These results show that growth factor context determines the topology of the MAPK signalling network and that the resulting dynamics govern cell fate. ..
  63. Sobczak I, Galabova Kovacs G, Sadzak I, Kren A, Christofori G, Baccarini M. B-Raf is required for ERK activation and tumor progression in a mouse model of pancreatic beta-cell carcinogenesis. Oncogene. 2008;27:4779-87 pubmed publisher
    ..signal-regulated kinase (ERK) pathway is required for the proliferation of cancer cell lines harboring activating BRAF or, to a lesser extent, activating RAS mutations...
  64. Ulisse S, Baldini E, Sorrenti S, Barollo S, Prinzi N, Catania A, et al. In papillary thyroid carcinoma BRAFV600E is associated with increased expression of the urokinase plasminogen activator and its cognate receptor, but not with disease-free interval. Clin Endocrinol (Oxf). 2012;77:780-6 pubmed publisher
    It has been suggested that patients with papillary thyroid cancer (PTC) harbouring the BRAF(V600E) mutation have a worse prognosis...
  65. Pao W, Girard N. New driver mutations in non-small-cell lung cancer. Lancet Oncol. 2011;12:175-80 pubmed publisher
    ..elsewhere, here, we discuss subsets defined by so-called driver mutations in ALK, HER2 (also known as ERBB2), BRAF, PIK3CA, AKT1, MAP2K1, and MET...
  66. Wojnowski L, Zimmer A, Beck T, Hahn H, Bernal R, Rapp U, et al. Endothelial apoptosis in Braf-deficient mice. Nat Genet. 1997;16:293-7 pubmed
    ..Here we show that mice with a targeted disruption in the Braf gene die of vascular defects during mid-gestation. Braf -/- embryos, unlike Araf -/- or Craf1 -/- embryos (L.W...