The mitogen-activated protein kinase (MAPK) pathway.[1][2][3][4][5][6][7][8][9][10] RAF-1 is between RAS and MEK just above the centre of the diagram.

RAF kinases are a family of three serine/threonine-specific protein kinases that are related to retroviral oncogenes.[11] The mouse sarcoma virus 3611 contains a RAF kinase-related oncogene that enhances fibrosarcoma induction. RAF is an acronym for Rapidly Accelerated Fibrosarcoma.[12]

RAF kinases participate in the RAS-RAF-MEK-ERK signal transduction cascade, also referred to as the mitogen-activated protein kinase (MAPK) cascade.[11] Activation of RAF kinases requires interaction with RAS-GTPases.

The three RAF kinase family members are:

References

  1. ↑ Rossomando AJ, Payne DM, Weber MJ, Sturgill TW (September 1989). "Evidence that pp42, a major tyrosine kinase target protein, is a mitogen-activated serine/threonine protein kinase". Proceedings of the National Academy of Sciences of the United States of America. 86 (18): 6940–6943. doi:10.1073/pnas.86.18.6940. PMC 297966. PMID 2550926.
  2. ↑ Bonni A, Brunet A, West AE, Datta SR, Takasu MA, Greenberg ME (November 1999). "Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and -independent mechanisms". Science. 286 (5443): 1358–1362. doi:10.1126/science.286.5443.1358. PMID 10558990.
  3. ↑ Chadee DN, Yuasa T, Kyriakis JM (February 2002). "Direct activation of mitogen-activated protein kinase kinase kinase MEKK1 by the Ste20p homologue GCK and the adapter protein TRAF2". Molecular and Cellular Biology. 22 (3): 737–749. doi:10.1128/MCB.22.3.737-749.2002. PMC 133545. PMID 11784851.
  4. ↑ Chang L, Karin M (March 2001). "Mammalian MAP kinase signalling cascades". Nature. 410 (6824): 37–40. doi:10.1038/35065000. PMID 11242034. S2CID 4407701.
  5. ↑ Chen YR, Tan TH (April 2000). "The c-Jun N-terminal kinase pathway and apoptotic signaling (review)". International Journal of Oncology. 16 (4): 651–662. doi:10.3892/ijo.16.4.651. PMID 10717232.
  6. ↑ Hazzalin CA, Mahadevan LC (January 2002). "MAPK-regulated transcription: a continuously variable gene switch?". Nature Reviews. Molecular Cell Biology. 3 (1): 30–40. doi:10.1038/nrm715. PMID 11823796. S2CID 23168636.
  7. ↑ Kato Y, Kravchenko VV, Tapping RI, Han J, Ulevitch RJ, Lee JD (December 1997). "BMK1/ERK5 regulates serum-induced early gene expression through transcription factor MEF2C". The EMBO Journal. 16 (23): 7054–7066. doi:10.1093/emboj/16.23.7054. PMC 1170308. PMID 9384584.
  8. ↑ Kiefer F, Tibbles LA, Anafi M, Janssen A, Zanke BW, Lassam N, et al. (December 1996). "HPK1, a hematopoietic protein kinase activating the SAPK/JNK pathway". The EMBO Journal. 15 (24): 7013–7025. doi:10.1002/j.1460-2075.1996.tb01093.x. PMC 452527. PMID 9003777.
  9. ↑ Pearson G, English JM, White MA, Cobb MH (March 2001). "ERK5 and ERK2 cooperate to regulate NF-kappaB and cell transformation". The Journal of Biological Chemistry. 276 (11): 7927–7931. doi:10.1074/jbc.M009764200. PMC 4372717. PMID 11118448.
  10. ↑ Weston CR, Lambright DG, Davis RJ (June 2002). "Signal transduction. MAP kinase signaling specificity". Science. 296 (5577): 2345–2347. doi:10.1126/science.1073344. PMID 12089430. S2CID 93194160.
  11. 1 2 Roskoski R (August 2010). "RAF protein-serine/threonine kinases: structure and regulation". Biochemical and Biophysical Research Communications. 399 (3): 313–317. doi:10.1016/j.bbrc.2010.07.092. PMID 20674547.
  12. ↑ Zebisch A, Troppmair J (June 2006). "Back to the roots: the remarkable RAF oncogene story". Cellular and Molecular Life Sciences. 63 (11): 1314–1330. doi:10.1007/s00018-006-6005-y. PMID 16649144. S2CID 20116800.
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