RAF kinase

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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

^ 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. Bibcode:1989PNAS...86.6940R. doi:10.1073/pnas.86.18.6940. PMC 297966. PMID 2550926.
^ 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.
^ 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.
^ Chang L, Karin M (March 2001). "Mammalian MAP kinase signalling cascades". Nature. 410 (6824): 37–40. doi:10.1038/35065000. PMID 11242034. S2CID 4407701.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ ^a ^b 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.
^ 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. PMC 11136008. PMID 16649144. S2CID 20116800.

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[pmid10558990-1] 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. Bibcode:1989PNAS...86.6940R. doi:10.1073/pnas.86.18.6940. PMC 297966. PMID 2550926.

[pmid2550926-2] 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.

[pmid11784851-3] 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.

[pmid11242034-4] Chang L, Karin M (March 2001). "Mammalian MAP kinase signalling cascades". Nature. 410 (6824): 37–40. doi:10.1038/35065000. PMID 11242034. S2CID 4407701.

[pmid10717232-5] 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.

[pmid11823796-6] 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.

[pmid9384584-7] 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.

[pmid9003777-8] 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.

[pmid11118448-9] 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.

[pmid12089430-10] 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.

[pmid20674547-11] 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.

[pmid16649144-12] 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. PMC 11136008. PMID 16649144. S2CID 20116800.

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v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)