RAF proto-oncogene serine/threonine-protein kinase

NameRAF proto-oncogene serine/threonine-protein kinase
Synonyms
  • 2.7.11.1
  • cRaf
  • Proto-oncogene c-RAF
  • RAF
  • Raf-1
Gene NameRAF1
OrganismHuman
Amino acid sequence
>lcl|BSEQ0000072|RAF proto-oncogene serine/threonine-protein kinase
MEHIQGAWKTISNGFGFKDAVFDGSSCISPTIVQQFGYQRRASDDGKLTDPSKTSNTIRV
FLPNKQRTVVNVRNGMSLHDCLMKALKVRGLQPECCAVFRLLHEHKGKKARLDWNTDAAS
LIGEELQVDFLDHVPLTTHNFARKTFLKLAFCDICQKFLLNGFRCQTCGYKFHEHCSTKV
PTMCVDWSNIRQLLLFPNSTIGDSGVPALPSLTMRRMRESVSRMPVSSQHRYSTPHAFTF
NTSSPSSEGSLSQRQRSTSTPNVHMVSTTLPVDSRMIEDAIRSHSESASPSALSSSPNNL
SPTGWSQPKTPVPAQRERAPVSGTQEKNKIRPRGQRDSSYYWEIEASEVMLSTRIGSGSF
GTVYKGKWHGDVAVKILKVVDPTPEQFQAFRNEVAVLRKTRHVNILLFMGYMTKDNLAIV
TQWCEGSSLYKHLHVQETKFQMFQLIDIARQTAQGMDYLHAKNIIHRDMKSNNIFLHEGL
TVKIGDFGLATVKSRWSGSQQVEQPTGSVLWMAPEVIRMQDNNPFSFQSDVYSYGIVLYE
LMTGELPYSHINNRDQIIFMVGRGYASPDLSKLYKNCPKAMKRLVADCVKKVKEERPLFP
QILSSIELLQHSLPKINRSASEPSLHRAAHTEDINACTLTTSPRLPVF
Number of residues648
Molecular Weight73051.025
Theoretical pI9.62
GO Classification
Functions
  • ATP binding
  • protein kinase activity
  • protein serine/threonine kinase activity
  • identical protein binding
  • MAP kinase kinase kinase activity
  • metal ion binding
Processes
  • fibroblast growth factor receptor signaling pathway
  • regulation of cell differentiation
  • Ras protein signal transduction
  • heart development
  • regulation of Rho protein signal transduction
  • signal transduction
  • insulin receptor signaling pathway
  • regulation of apoptotic process
  • response to hypoxia
  • insulin secretion involved in cellular response to glucose stimulus
  • response to muscle stretch
  • intermediate filament cytoskeleton organization
  • axon guidance
  • somatic stem cell population maintenance
  • ion transmembrane transport
  • epidermal growth factor receptor signaling pathway
  • stimulatory C-type lectin receptor signaling pathway
  • blood coagulation
  • MAPK cascade
  • innate immune response
  • vascular endothelial growth factor receptor signaling pathway
  • wound healing
  • negative regulation of apoptotic process
  • Fc-epsilon receptor signaling pathway
  • negative regulation of cell proliferation
  • transmembrane transport
  • small GTPase mediated signal transduction
  • negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
  • synaptic transmission
  • negative regulation of extrinsic apoptotic signaling pathway via death domain receptors
  • negative regulation of protein complex assembly
  • activation of adenylate cyclase activity
  • platelet activation
  • neurotrophin TRK receptor signaling pathway
  • activation of MAPKK activity
  • regulation of cell motility
  • positive regulation of peptidyl-serine phosphorylation
  • apoptotic process
  • cell proliferation
  • positive regulation of transcription from RNA polymerase II promoter
  • death-inducing signaling complex assembly
  • protein phosphorylation
Components
  • cytoplasm
  • Golgi apparatus
  • cytosol
  • nucleus
  • plasma membrane
  • pseudopodium
  • mitochondrial outer membrane
General FunctionProtein serine/threonine kinase activity
Specific FunctionSerine/threonine-protein kinase that acts as a regulatory link between the membrane-associated Ras GTPases and the MAPK/ERK cascade, and this critical regulatory link functions as a switch determining cell fate decisions including proliferation, differentiation, apoptosis, survival and oncogenic transformation. RAF1 activation initiates a mitogen-activated protein kinase (MAPK) cascade that comprises a sequential phosphorylation of the dual-specific MAPK kinases (MAP2K1/MEK1 and MAP2K2/MEK2) and the extracellular signal-regulated kinases (MAPK3/ERK1 and MAPK1/ERK2). The phosphorylated form of RAF1 (on residues Ser-338 and Ser-339, by PAK1) phosphorylates BAD/Bcl2-antagonist of cell death at 'Ser-75'. Phosphorylates adenylyl cyclases: ADCY2, ADCY5 and ADCY6, resulting in their activation. Phosphorylates PPP1R12A resulting in inhibition of the phosphatase activity. Phosphorylates TNNT2/cardiac muscle troponin T. Can promote NF-kB activation and inhibit signal transducers involved in motility (ROCK2), apoptosis (MAP3K5/ASK1 and STK3/MST2), proliferation and angiogenesis (RB1). Can protect cells from apoptosis also by translocating to the mitochondria where it binds BCL2 and displaces BAD/Bcl2-antagonist of cell death. Regulates Rho signaling and migration, and is required for normal wound healing. Plays a role in the oncogenic transformation of epithelial cells via repression of the TJ protein, occludin (OCLN) by inducing the up-regulation of a transcriptional repressor SNAI2/SLUG, which induces down-regulation of OCLN. Restricts caspase activation in response to selected stimuli, notably Fas stimulation, pathogen-mediated macrophage apoptosis, and erythroid differentiation.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID35842
UniProtKB IDP04049
UniProtKB Entry NameRAF1_HUMAN
Cellular LocationCytoplasm
Gene sequence
>lcl|BSEQ0009890|RAF proto-oncogene serine/threonine-protein kinase (RAF1)
ATGGAGCACATACAGGGAGCTTGGAAGACGATCAGCAATGGTTTTGGATTCAAAGATGCC
GTGTTTGATGGCTCCAGCTGCATCTCTCCTACAATAGTTCAGCAGTTTGGCTATCAGCGC
CGGGCATCAGATGATGGCAAACTCACAGATCCTTCTAAGACAAGCAACACTATCCGTGTT
TTCTTGCCGAACAAGCAAAGAACAGTGGTCAATGTGCGAAATGGAATGAGCTTGCATGAC
TGCCTTATGAAAGCACTCAAGGTGAGGGGCCTGCAACCAGAGTGCTGTGCAGTGTTCAGA
CTTCTCCACGAACACAAAGGTAAAAAAGCACGCTTAGATTGGAATACTGATGCTGCGTCT
TTGATTGGAGAAGAACTTCAAGTAGATTTCCTGGATCATGTTCCCCTCACAACACACAAC
TTTGCTCGGAAGACGTTCCTGAAGCTTGCCTTCTGTGACATCTGTCAGAAATTCCTGCTC
AATGGATTTCGATGTCAGACTTGTGGCTACAAATTTCATGAGCACTGTAGCACCAAAGTA
CCTACTATGTGTGTGGACTGGAGTAACATCAGACAACTCTTATTGTTTCCAAATTCCACT
ATTGGTGATAGTGGAGTCCCAGCACTACCTTCTTTGACTATGCGTCGTATGCGAGAGTCT
GTTTCCAGGATGCCTGTTAGTTCTCAGCACAGATATTCTACACCTCACGCCTTCACCTTT
AACACCTCCAGTCCCTCATCTGAAGGTTCCCTCTCCCAGAGGCAGAGGTCGACATCCACA
CCTAATGTCCACATGGTCAGCACCACCCTGCCTGTGGACAGCAGGATGATTGAGGATGCA
ATTCGAAGTCACAGCGAATCAGCCTCACCTTCAGCCCTGTCCAGTAGCCCCAACAATCTG
AGCCCAACAGGCTGGTCACAGCCGAAAACCCCCGTGCCAGCACAAAGAGAGCGGGCACCA
GTATCTGGGACCCAGGAGAAAAACAAAATTAGGCCTCGTGGACAGAGAGATTCAAGCTAT
TATTGGGAAATAGAAGCCAGTGAAGTGATGCTGTCCACTCGGATTGGGTCAGGCTCTTTT
GGAACTGTTTATAAGGGTAAATGGCACGGAGATGTTGCAGTAAAGATCCTAAAGGTTGTC
GACCCAACCCCAGAGCAATTCCAGGCCTTCAGGAATGAGGTGGCTGTTCTGCGCAAAACA
CGGCATGTGAACATTCTGCTTTTCATGGGGTACATGACAAAGGACAACCTGGCAATTGTG
ACCCAGTGGTGCGAGGGCAGCAGCCTCTACAAACACCTGCATGTCCAGGAGACCAAGTTT
CAGATGTTCCAGCTAATTGACATTGCCCGGCAGACGGCTCAGGGAATGGACTATTTGCAT
GCAAAGAACATCATCCATAGAGACATGAAATCCAACAATATATTTCTCCATGAAGGCTTA
ACAGTGAAAATTGGAGATTTTGGTTTGGCAACAGTAAAGTCACGCTGGAGTGGTTCTCAG
CAGGTTGAACAACCTACTGGCTCTGTCCTCTGGATGGCCCCAGAGGTGATCCGAATGCAG
GATAACAACCCATTCAGTTTCCAGTCGGATGTCTACTCCTATGGCATCGTATTGTATGAA
CTGATGACGGGGGAGCTTCCTTATTCTCACATCAACAACCGAGATCAGATCATCTTCATG
GTGGGCCGAGGATATGCCTCCCCAGATCTTAGTAAGCTATATAAGAACTGCCCCAAAGCA
ATGAAGAGGCTGGTAGCTGACTGTGTGAAGAAAGTAAAGGAAGAGAGGCCTCTTTTTCCC
CAGATCCTGTCTTCCATTGAGCTGCTCCAACACTCTCTACCGAAGATCAACCGGAGCGCT
TCCGAGCCATCCTTGCATCGGGCAGCCCACACTGAGGATATCAATGCTTGCACGCTGACC
ACGTCCCCGAGGCTGCCTGTCTTCTAG
GenBank Gene IDX03484
GeneCard IDNot Available
GenAtlas IDRAF1
HGNC IDHGNC:9829
Chromosome Location3
Locus3p25
References
  1. Bonner TI, Oppermann H, Seeburg P, Kerby SB, Gunnell MA, Young AC, Rapp UR: The complete coding sequence of the human raf oncogene and the corresponding structure of the c-raf-1 gene. Nucleic Acids Res. 1986 Jan 24;14(2):1009-15. 3003687
  2. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. 14702039
  3. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  4. Bonner TI, Kerby SB, Sutrave P, Gunnell MA, Mark G, Rapp UR: Structure and biological activity of human homologs of the raf/mil oncogene. Mol Cell Biol. 1985 Jun;5(6):1400-7. 2993863
  5. Andreu-Perez P, Esteve-Puig R, de Torre-Minguela C, Lopez-Fauqued M, Bech-Serra JJ, Tenbaum S, Garcia-Trevijano ER, Canals F, Merlino G, Avila MA, Recio JA: Protein arginine methyltransferase 5 regulates ERK1/2 signal transduction amplitude and cell fate through CRAF. Sci Signal. 2011 Sep 13;4(190):ra58. doi: 10.1126/scisignal.2001936. 21917714
  6. Yao B, Zhang Y, Delikat S, Mathias S, Basu S, Kolesnick R: Phosphorylation of Raf by ceramide-activated protein kinase. Nature. 1995 Nov 16;378(6554):307-10. 7477354
  7. Dozier C, Ansieau S, Ferreira E, Coll J, Stehelin D: An alternatively spliced c-mil/raf mRNA is predominantly expressed in chicken muscular tissues and conserved among vertebrate species. Oncogene. 1991 Aug;6(8):1307-11. 1886707
  8. Morrison DK, Heidecker G, Rapp UR, Copeland TD: Identification of the major phosphorylation sites of the Raf-1 kinase. J Biol Chem. 1993 Aug 15;268(23):17309-16. 8349614
  9. Dubois T, Rommel C, Howell S, Steinhussen U, Soneji Y, Morrice N, Moelling K, Aitken A: 14-3-3 is phosphorylated by casein kinase I on residue 233. Phosphorylation at this site in vivo regulates Raf/14-3-3 interaction. J Biol Chem. 1997 Nov 14;272(46):28882-8. 9360956
  10. King AJ, Sun H, Diaz B, Barnard D, Miao W, Bagrodia S, Marshall MS: The protein kinase Pak3 positively regulates Raf-1 activity through phosphorylation of serine 338. Nature. 1998 Nov 12;396(6707):180-3. 9823899
  11. Zimmermann S, Moelling K: Phosphorylation and regulation of Raf by Akt (protein kinase B). Science. 1999 Nov 26;286(5445):1741-4. 10576742
  12. Abraham D, Podar K, Pacher M, Kubicek M, Welzel N, Hemmings BA, Dilworth SM, Mischak H, Kolch W, Baccarini M: Raf-1-associated protein phosphatase 2A as a positive regulator of kinase activation. J Biol Chem. 2000 Jul 21;275(29):22300-4. 10801873
  13. Chong H, Lee J, Guan KL: Positive and negative regulation of Raf kinase activity and function by phosphorylation. EMBO J. 2001 Jul 16;20(14):3716-27. 11447113
  14. Chen J, Fujii K, Zhang L, Roberts T, Fu H: Raf-1 promotes cell survival by antagonizing apoptosis signal-regulating kinase 1 through a MEK-ERK independent mechanism. Proc Natl Acad Sci U S A. 2001 Jul 3;98(14):7783-8. Epub 2001 Jun 26. 11427728
  15. Broustas CG, Grammatikakis N, Eto M, Dent P, Brautigan DL, Kasid U: Phosphorylation of the myosin-binding subunit of myosin phosphatase by Raf-1 and inhibition of phosphatase activity. J Biol Chem. 2002 Jan 25;277(4):3053-9. Epub 2001 Nov 21. 11719507
  16. Zang M, Hayne C, Luo Z: Interaction between active Pak1 and Raf-1 is necessary for phosphorylation and activation of Raf-1. J Biol Chem. 2002 Feb 8;277(6):4395-405. Epub 2001 Nov 30. 11733498
  17. Kubicek M, Pacher M, Abraham D, Podar K, Eulitz M, Baccarini M: Dephosphorylation of Ser-259 regulates Raf-1 membrane association. J Biol Chem. 2002 Mar 8;277(10):7913-9. Epub 2001 Dec 27. 11756411
  18. Wang Y, Waldron RT, Dhaka A, Patel A, Riley MM, Rozengurt E, Colicelli J: The RAS effector RIN1 directly competes with RAF and is regulated by 14-3-3 proteins. Mol Cell Biol. 2002 Feb;22(3):916-26. 11784866
  19. Sasaki A, Taketomi T, Kato R, Saeki K, Nonami A, Sasaki M, Kuriyama M, Saito N, Shibuya M, Yoshimura A: Mammalian Sprouty4 suppresses Ras-independent ERK activation by binding to Raf1. Nat Cell Biol. 2003 May;5(5):427-32. 12717443
  20. Kunapuli P, Kasyapa CS, Hawthorn L, Cowell JK: LGI1, a putative tumor metastasis suppressor gene, controls in vitro invasiveness and expression of matrix metalloproteinases in glioma cells through the ERK1/2 pathway. J Biol Chem. 2004 May 28;279(22):23151-7. Epub 2004 Mar 26. 15047712
  21. Ding Q, Gros R, Gray ID, Taussig R, Ferguson SS, Feldman RD: Raf kinase activation of adenylyl cyclases: isoform-selective regulation. Mol Pharmacol. 2004 Oct;66(4):921-8. 15385642
  22. O'Neill E, Rushworth L, Baccarini M, Kolch W: Role of the kinase MST2 in suppression of apoptosis by the proto-oncogene product Raf-1. Science. 2004 Dec 24;306(5705):2267-70. 15618521
  23. Cho YJ, Abe M, Kim SY, Sato Y: Raf-1 is a binding partner of DSCR1. Arch Biochem Biophys. 2005 Jul 1;439(1):121-8. 15935327
  24. Baccarini M: Second nature: biological functions of the Raf-1 "kinase". FEBS Lett. 2005 Jun 13;579(15):3271-7. Epub 2005 Mar 23. 15943972
  25. Jin S, Zhuo Y, Guo W, Field J: p21-activated Kinase 1 (Pak1)-dependent phosphorylation of Raf-1 regulates its mitochondrial localization, phosphorylation of BAD, and Bcl-2 association. J Biol Chem. 2005 Jul 1;280(26):24698-705. Epub 2005 Apr 22. 15849194
  26. Zhu J, Balan V, Bronisz A, Balan K, Sun H, Leicht DT, Luo Z, Qin J, Avruch J, Tzivion G: Identification of Raf-1 S471 as a novel phosphorylation site critical for Raf-1 and B-Raf kinase activities and for MEK binding. Mol Biol Cell. 2005 Oct;16(10):4733-44. Epub 2005 Aug 10. 16093354
  27. Rodriguez-Viciana P, Oses-Prieto J, Burlingame A, Fried M, McCormick F: A phosphatase holoenzyme comprised of Shoc2/Sur8 and the catalytic subunit of PP1 functions as an M-Ras effector to modulate Raf activity. Mol Cell. 2006 Apr 21;22(2):217-30. 16630891
  28. Rushworth LK, Hindley AD, O'Neill E, Kolch W: Regulation and role of Raf-1/B-Raf heterodimerization. Mol Cell Biol. 2006 Mar;26(6):2262-72. 16508002
  29. von Kriegsheim A, Pitt A, Grindlay GJ, Kolch W, Dhillon AS: Regulation of the Raf-MEK-ERK pathway by protein phosphatase 5. Nat Cell Biol. 2006 Sep;8(9):1011-6. Epub 2006 Aug 6. 16892053
  30. Dhillon AS, von Kriegsheim A, Grindlay J, Kolch W: Phosphatase and feedback regulation of Raf-1 signaling. Cell Cycle. 2007 Jan 1;6(1):3-7. Epub 2007 Jan 9. 17218791
  31. Wang Z, Wade P, Mandell KJ, Akyildiz A, Parkos CA, Mrsny RJ, Nusrat A: Raf 1 represses expression of the tight junction protein occludin via activation of the zinc-finger transcription factor slug. Oncogene. 2007 Feb 22;26(8):1222-30. Epub 2006 Aug 21. 16924233
  32. Matsuoka S, Ballif BA, Smogorzewska A, McDonald ER 3rd, Hurov KE, Luo J, Bakalarski CE, Zhao Z, Solimini N, Lerenthal Y, Shiloh Y, Gygi SP, Elledge SJ: ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science. 2007 May 25;316(5828):1160-6. 17525332
  33. Rath O, Park S, Tang HH, Banfield MJ, Brady RL, Lee YC, Dignam JD, Sedivy JM, Kolch W, Yeung KC: The RKIP (Raf-1 Kinase Inhibitor Protein) conserved pocket binds to the phosphorylated N-region of Raf-1 and inhibits the Raf-1-mediated activated phosphorylation of MEK. Cell Signal. 2008 May;20(5):935-41. doi: 10.1016/j.cellsig.2008.01.012. Epub 2008 Jan 24. 18294816
  34. Wu X, Carr HS, Dan I, Ruvolo PP, Frost JA: p21 activated kinase 5 activates Raf-1 and targets it to mitochondria. J Cell Biochem. 2008 Sep 1;105(1):167-75. doi: 10.1002/jcb.21809. 18465753
  35. Cantin GT, Yi W, Lu B, Park SK, Xu T, Lee JD, Yates JR 3rd: Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis. J Proteome Res. 2008 Mar;7(3):1346-51. doi: 10.1021/pr0705441. Epub 2008 Jan 26. 18220336
  36. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. 18691976
  37. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. 18669648
  38. Smith J, Bunaciu RP, Reiterer G, Coder D, George T, Asaly M, Yen A: Retinoic acid induces nuclear accumulation of Raf1 during differentiation of HL-60 cells. Exp Cell Res. 2009 Aug 1;315(13):2241-8. doi: 10.1016/j.yexcr.2009.03.004. Epub 2009 Mar 17. 19298812
  39. Yasuda S, Kai M, Imai S, Takeishi K, Taketomi A, Toyota M, Kanoh H, Sakane F: Diacylglycerol kinase eta augments C-Raf activity and B-Raf/C-Raf heterodimerization. J Biol Chem. 2009 Oct 23;284(43):29559-70. doi: 10.1074/jbc.M109.043604. Epub 2009 Aug 26. 19710016
  40. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. 19690332
  41. Roskoski R Jr: RAF protein-serine/threonine kinases: structure and regulation. Biochem Biophys Res Commun. 2010 Aug 27;399(3):313-7. doi: 10.1016/j.bbrc.2010.07.092. Epub 2010 Jul 30. 20674547
  42. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. 20068231
  43. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. 21269460
  44. Matallanas D, Birtwistle M, Romano D, Zebisch A, Rauch J, von Kriegsheim A, Kolch W: Raf family kinases: old dogs have learned new tricks. Genes Cancer. 2011 Mar;2(3):232-60. doi: 10.1177/1947601911407323. 21779496
  45. Rigbolt KT, Prokhorova TA, Akimov V, Henningsen J, Johansen PT, Kratchmarova I, Kassem M, Mann M, Olsen JV, Blagoev B: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci Signal. 2011 Mar 15;4(164):rs3. doi: 10.1126/scisignal.2001570. 21406692
  46. Cipriano R, Graham J, Miskimen KL, Bryson BL, Bruntz RC, Scott SA, Brown HA, Stark GR, Jackson MW: FAM83B mediates EGFR- and RAS-driven oncogenic transformation. J Clin Invest. 2012 Sep;122(9):3197-210. doi: 10.1172/JCI60517. Epub 2012 Aug 13. 22886302
  47. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. 24275569
  48. Nassar N, Horn G, Herrmann C, Scherer A, McCormick F, Wittinghofer A: The 2.2 A crystal structure of the Ras-binding domain of the serine/threonine kinase c-Raf1 in complex with Rap1A and a GTP analogue. Nature. 1995 Jun 15;375(6532):554-60. 7791872
  49. Nassar N, Horn G, Herrmann C, Block C, Janknecht R, Wittinghofer A: Ras/Rap effector specificity determined by charge reversal. Nat Struct Biol. 1996 Aug;3(8):723-9. 8756332
  50. Emerson SD, Madison VS, Palermo RE, Waugh DS, Scheffler JE, Tsao KL, Kiefer SE, Liu SP, Fry DC: Solution structure of the Ras-binding domain of c-Raf-1 and identification of its Ras interaction surface. Biochemistry. 1995 May 30;34(21):6911-8. 7766599
  51. Mott HR, Carpenter JW, Zhong S, Ghosh S, Bell RM, Campbell SL: The solution structure of the Raf-1 cysteine-rich domain: a novel ras and phospholipid binding site. Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8312-7. 8710867
  52. Pandit B, Sarkozy A, Pennacchio LA, Carta C, Oishi K, Martinelli S, Pogna EA, Schackwitz W, Ustaszewska A, Landstrom A, Bos JM, Ommen SR, Esposito G, Lepri F, Faul C, Mundel P, Lopez Siguero JP, Tenconi R, Selicorni A, Rossi C, Mazzanti L, Torrente I, Marino B, Digilio MC, Zampino G, Ackerman MJ, Dallapiccola B, Tartaglia M, Gelb BD: Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy. Nat Genet. 2007 Aug;39(8):1007-12. Epub 2007 Jul 1. 17603483
  53. Razzaque MA, Nishizawa T, Komoike Y, Yagi H, Furutani M, Amo R, Kamisago M, Momma K, Katayama H, Nakagawa M, Fujiwara Y, Matsushima M, Mizuno K, Tokuyama M, Hirota H, Muneuchi J, Higashinakagawa T, Matsuoka R: Germline gain-of-function mutations in RAF1 cause Noonan syndrome. Nat Genet. 2007 Aug;39(8):1013-7. Epub 2007 Jul 1. 17603482
  54. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. 17344846
  55. Longoni M, Moncini S, Cisternino M, Morella IM, Ferraiuolo S, Russo S, Mannarino S, Brazzelli V, Coi P, Zippel R, Venturin M, Riva P: Noonan syndrome associated with both a new Jnk-activating familial SOS1 and a de novo RAF1 mutations. Am J Med Genet A. 2010 Sep;152A(9):2176-84. doi: 10.1002/ajmg.a.33564. 20683980
  56. Dhandapany PS, Razzaque MA, Muthusami U, Kunnoth S, Edwards JJ, Mulero-Navarro S, Riess I, Pardo S, Sheng J, Rani DS, Rani B, Govindaraj P, Flex E, Yokota T, Furutani M, Nishizawa T, Nakanishi T, Robbins J, Limongelli G, Hajjar RJ, Lebeche D, Bahl A, Khullar M, Rathinavel A, Sadler KC, Tartaglia M, Matsuoka R, Thangaraj K, Gelb BD: RAF1 mutations in childhood-onset dilated cardiomyopathy. Nat Genet. 2014 Jun;46(6):635-9. doi: 10.1038/ng.2963. Epub 2014 Apr 28. 24777450