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Gene Review

Braf  -  Braf transforming gene

Mus musculus

Synonyms: 9930012E13Rik, AA120551, AA387315, AA473386, B-raf, ...
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Disease relevance of Braf

  • Furthermore, constitutive expression of B-raf in astrocytoma cells increased MAPK activation, as seen in neurons, and enhanced proliferation [1].

High impact information on Braf

  • In addition, neither ERK phosphorylation nor development are affected in B-raf-deficient embryos that are born alive obtained by epiblast-restricted gene inactivation [2].
  • Structure and sequence analysis of the cDNA clones revealed that the oncogene was created by recombinational events involving an unknown gene and the mouse homologue of the B-raf protooncogene [3].
  • Phosphorylation of the myosin light chain on Thr18/Ser19 residues was not reduced in B-raf(-/-) cells [4].
  • We have analyzed the migratory characteristics of B-raf(-/-) mouse embryonic fibroblasts (MEFs) and compared these with the organization of the actin cytoskeleton and the activity of signaling pathways that are known to influence this organization [4].
  • Disruption of B-raf significantly reduced the levels of phospho-ERK1/2 and, surprisingly, induced an approximately 1.5-fold increase in cell migration [4].

Biological context of Braf

  • In contrast to human nevi, these nevi lacked hotspot mutations in Braf or Ras genes, possibly explaining the lack of malignant progression in the Ink4a/Arf(-/-) mice [5].
  • Here we describe the phenotype of mouse mutants with different combinations of mutant Craf-1 and Braf alleles [6].
  • Overlapping and specific functions of Braf and Craf-1 proto-oncogenes during mouse embryogenesis [6].
  • The c-Rmil/B-raf proto-oncogene is a member of the mil/raf family encoding serine/threonine protein kinases shown to be involved in signal transduction from the membrane to the nucleus [7].
  • We isolated from a mouse brain library B-raf cDNAs containing a previously unidentified 36-base pair alternatively spliced exon located between exons 8 and 9 and, therefore, designated exon 8b [7].

Anatomical context of Braf

  • B-raf was found to have a very restricted expression pattern, with high levels in fetal brain and adult cerebrum [8].
  • In addition to the 10 and 13 kb transcripts common to all B-raf expressing tissues, alternate sized B-raf RNAs were detected in testes, placenta and fetal membranes [8].
  • Consistent with these findings, the high level of actin stress fibers normally present in MEFs was considerably reduced following disruption of B-raf, and the F-actin content of B-raf(-/-) cells was less than half that of B-raf(+/+) cells [4].
  • We found that central nervous system-derived neurons, but not astrocytes, express B-raf [1].
  • In contrast, B-raf is expressed as two major transcripts of 4.0 and 2.6 kb, with the 4.0-kb transcript first expressed at low levels in pachytene spermatocytes and the more abundant 2.6-kb transcript restricted to post-meiotic spermatids [9].

Associations of Braf with chemical compounds

  • These data provide the first experimental evidence that B-raf is the molecular switch which dominantly permits differential cAMP-dependent regulation of MAPK in neurons versus astrocytes, with important implications for both survival and proliferation [1].
  • The proto-oncogene c-raf-1 and the related genes A-raf and B-raf encode serine/threonine protein kinases thought to be involved in regulating gene expression by transducing extracellular signals into the cell [9].

Other interactions of Braf

  • However, due to a significant redundancy between Craf-1 and Braf, either gene is sufficient for normal development until mid-gestation [6].
  • Yet Ras genes and Braf, while often activated in cancer cells, are infrequent targets for activation in neuroblastoma [10].
  • Ha-ras- and B-raf-mutated liver tumors were rare and not significantly different between treatment groups [11].
  • Our findings demonstrate that B-raf plays a role in hippocampal ERK activation, synaptic plasticity, and L&M [12].

Analytical, diagnostic and therapeutic context of Braf


  1. Differential effects of cAMP in neurons and astrocytes. Role of B-raf. Dugan, L.L., Kim, J.S., Zhang, Y., Bart, R.D., Sun, Y., Holtzman, D.M., Gutmann, D.H. J. Biol. Chem. (1999) [Pubmed]
  2. Essential role of B-Raf in ERK activation during extraembryonic development. Galabova-Kovacs, G., Matzen, D., Piazzolla, D., Meissl, K., Plyushch, T., Chen, A.P., Silva, A., Baccarini, M. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  3. Development of a highly efficient expression cDNA cloning system: application to oncogene isolation. Miki, T., Fleming, T.P., Crescenzi, M., Molloy, C.J., Blam, S.B., Reynolds, S.H., Aaronson, S.A. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  4. B-Raf acts via the ROCKII/LIMK/cofilin pathway to maintain actin stress fibers in fibroblasts. Pritchard, C.A., Hayes, L., Wojnowski, L., Zimmer, A., Marais, R.M., Norman, J.C. Mol. Cell. Biol. (2004) [Pubmed]
  5. Induction of nevi and skin tumors in Ink4a/Arf Xpa knockout mice by neonatal, intermittent, or chronic UVB exposures. van Schanke, A., van Venrooij, G.M., Jongsma, M.J., Banus, H.A., Mullenders, L.H., van Kranen, H.J., de Gruijl, F.R. Cancer Res. (2006) [Pubmed]
  6. Overlapping and specific functions of Braf and Craf-1 proto-oncogenes during mouse embryogenesis. Wojnowski, L., Stancato, L.F., Larner, A.C., Rapp, U.R., Zimmer, A. Mech. Dev. (2000) [Pubmed]
  7. The mouse B-raf gene encodes multiple protein isoforms with tissue-specific expression. Barnier, J.V., Papin, C., Eychène, A., Lecoq, O., Calothy, G. J. Biol. Chem. (1995) [Pubmed]
  8. Expression of raf family proto-oncogenes in normal mouse tissues. Storm, S.M., Cleveland, J.L., Rapp, U.R. Oncogene (1990) [Pubmed]
  9. Developmental and cell lineage specificity of raf family gene expression in mouse testis. Wadewitz, A.G., Winer, M.A., Wolgemuth, D.J. Oncogene (1993) [Pubmed]
  10. Mutations in PIK3CA are infrequent in neuroblastoma. Dam, V., Morgan, B.T., Mazanek, P., Hogarty, M.D. BMC Cancer (2006) [Pubmed]
  11. PCB 153, a non-dioxin-like tumor promoter, selects for beta-catenin (Catnb)-mutated mouse liver tumors. Strathmann, J., Schwarz, M., Tharappel, J.C., Glauert, H.P., Spear, B.T., Robertson, L.W., Appel, K.E., Buchmann, A. Toxicol. Sci. (2006) [Pubmed]
  12. Forebrain-specific knockout of B-raf kinase leads to deficits in hippocampal long-term potentiation, learning, and memory. Chen, A.P., Ohno, M., Giese, K.P., Kühn, R., Chen, R.L., Silva, A.J. J. Neurosci. Res. (2006) [Pubmed]
  13. Members of the raf gene family exhibit segment-specific patterns of expression in mouse epididymis. Winer, M.A., Wadewitz, A.G., Wolgemuth, D.J. Mol. Reprod. Dev. (1993) [Pubmed]
  14. B-raf oncogene: activation by rearrangements and assignment to human chromosome 7. Kamiyama, T., Aoki, N., Yuasa, Y. Jpn. J. Cancer Res. (1993) [Pubmed]
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