C-Raf Proto Oncogene Serine/Threonine Protein Kinase (CRAF)

RAF1; Raf1; V-raf-1 Murine Leukemia Viral Oncogene Homolog 1; Proto-oncogene c-RAF

SPN	U613
HGNC	9829
MGI	97847
PubMed	7803760
RGD	3531
UniProt	P04049
Wiki	C-Raf

C-raf is gene that codes for a protein kinase. That protein is sometimes called c-Raf and will be called "Raf-1" here. The Raf-1 protein functions in the MAPK/ERK signal transduction pathway as part of a protein kinase cascade. Raf-1 is a serine/threonine-specific kinase.Raf-1 is a MAP kinase kinase kinase (MAP3K) which functions downstream of the Ras family of membrane associated GTPases to which it binds directly. Once activated Raf-1 can phosphorylate to activate the dual specificity protein kinases MEK1 and MEK2 which in turn phosphorylate to activate the serine/threonine specific protein kinases ERK1 and ERK2. Activated ERKs are pleiotropic effectors of cell physiology and play an important role in the control of gene expression involved in the cell division cycle, apoptosis, cell differentiation and cell migration.

Reference

"The complete coding sequence of the human raf oncogene and the corresponding structure of the c-raf-1 gene."
Nucleic Acids Res. 14:1009-1015(1986) [PubMed] [Europe PMC] [Abstract]

"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"Structure and biological activity of human homologs of the raf/mil oncogene."
Mol. Cell. Biol. 5:1400-1407(1985) [PubMed] [Europe PMC] [Abstract]

"Protein arginine methyltransferase 5 regulates ERK1/2 signal transduction amplitude and cell fate through CRAF."
Sci. Signal. 4:RA58-RA58(2011) [PubMed] [Europe PMC] [Abstract]

"Phosphorylation of Raf by ceramide-activated protein kinase."
Nature 378:307-310(1995) [PubMed] [Europe PMC] [Abstract]

"An alternatively spliced c-mil/raf mRNA is predominantly expressed in chicken muscular tissues and conserved among vertebrate species."
Oncogene 6:1307-1311(1991) [PubMed] [Europe PMC] [Abstract]

"Identification of the major phosphorylation sites of the Raf-1 kinase."
J. Biol. Chem. 268:17309-17316(1993) [PubMed] [Europe PMC] [Abstract]

"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. 272:28882-28888(1997) [PubMed] [Europe PMC] [Abstract]

"The protein kinase Pak3 positively regulates Raf-1 activity through phosphorylation of serine 338."
Nature 396:180-183(1998) [PubMed] [Europe PMC] [Abstract]

Erratum
Nature 406:439-439(2000)

"Phosphorylation and regulation of Raf by Akt (protein kinase B)."
Science 286:1741-1744(1999) [PubMed] [Europe PMC] [Abstract]

"Raf-1-associated protein phosphatase 2A as a positive regulator of kinase activation."
J. Biol. Chem. 275:22300-22304(2000) [PubMed] [Europe PMC] [Abstract]

"Positive and negative regulation of Raf kinase activity and function by phosphorylation."
EMBO J. 20:3716-3727(2001) [PubMed] [Europe PMC] [Abstract]

"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. 98:7783-7788(2001) [PubMed] [Europe PMC] [Abstract]

"Phosphorylation of the myosin-binding subunit of myosin phosphatase by Raf-1 and inhibition of phosphatase activity."
J. Biol. Chem. 277:3053-3059(2002) [PubMed] [Europe PMC] [Abstract]

"Interaction between active Pak1 and Raf-1 is necessary for phosphorylation and activation of Raf-1."
J. Biol. Chem. 277:4395-4405(2002) [PubMed] [Europe PMC] [Abstract]

"Dephosphorylation of Ser-259 regulates Raf-1 membrane association."
J. Biol. Chem. 277:7913-7919(2002) [PubMed] [Europe PMC] [Abstract]

"The RAS effector RIN1 directly competes with RAF and is regulated by 14-3-3 proteins."
Mol. Cell. Biol. 22:916-926(2002) [PubMed] [Europe PMC] [Abstract]

"Mammalian Sprouty4 suppresses Ras-independent ERK activation by binding to Raf1."
Nat. Cell Biol. 5:427-432(2003) [PubMed] [Europe PMC] [Abstract]

"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. 279:23151-23157(2004) [PubMed] [Europe PMC] [Abstract]

Erratum
J. Biol. Chem. 282:2752-2752(2007)

"Raf kinase activation of adenylyl cyclases: isoform-selective regulation."
Mol. Pharmacol. 66:921-928(2004) [PubMed] [Europe PMC] [Abstract]

"Role of the kinase MST2 in suppression of apoptosis by the proto-oncogene product Raf-1."
Science 306:2267-2270(2004) [PubMed] [Europe PMC] [Abstract]

"Raf-1 is a binding partner of DSCR1."
Arch. Biochem. Biophys. 439:121-128(2005) [PubMed] [Europe PMC] [Abstract]

"Second nature: biological functions of the Raf-1 'kinase'."
FEBS Lett. 579:3271-3277(2005) [PubMed] [Europe PMC] [Abstract]

"p21-activated Kinase 1 (Pak1)-dependent phosphorylation of Raf-1 regulates its mitochondrial localization, phosphorylation of BAD, and Bcl-2 association."
J. Biol. Chem. 280:24698-24705(2005) [PubMed] [Europe PMC] [Abstract]

"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 16:4733-4744(2005) [PubMed] [Europe PMC] [Abstract]

"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 22:217-230(2006) [PubMed] [Europe PMC] [Abstract]

"Regulation and role of Raf-1/B-Raf heterodimerization."
Mol. Cell. Biol. 26:2262-2272(2006) [PubMed] [Europe PMC] [Abstract]

"Regulation of the Raf-MEK-ERK pathway by protein phosphatase 5."
Nat. Cell Biol. 8:1011-1016(2006) [PubMed] [Europe PMC] [Abstract]

"Phosphatase and feedback regulation of Raf-1 signaling."
Cell Cycle 6:3-7(2007) [PubMed] [Europe PMC] [Abstract]

"Raf 1 represses expression of the tight junction protein occludin via activation of the zinc-finger transcription factor slug."
Oncogene 26:1222-1230(2007) [PubMed] [Europe PMC] [Abstract]

"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage."
Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract]

"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. 20:935-941(2008) [PubMed] [Europe PMC] [Abstract]

"p21 activated kinase 5 activates Raf-1 and targets it to mitochondria."
J. Cell. Biochem. 105:167-175(2008) [PubMed] [Europe PMC] [Abstract]

"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis."
J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract]

"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]

"A quantitative atlas of mitotic phosphorylation."
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]

"Retinoic acid induces nuclear accumulation of Raf1 during differentiation of HL-60 cells."
Exp. Cell Res. 315:2241-2248(2009) [PubMed] [Europe PMC] [Abstract]

"Diacylglycerol kinase eta augments C-Raf activity and B-Raf/C-Raf heterodimerization."
J. Biol. Chem. 284:29559-29570(2009) [PubMed] [Europe PMC] [Abstract]

"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]

"RAF protein-serine/threonine kinases: structure and regulation."
Biochem. Biophys. Res. Commun. 399:313-317(2010) [PubMed] [Europe PMC] [Abstract]

"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]

"Initial characterization of the human central proteome."
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]

"Raf family kinases: old dogs have learned new tricks."
Genes Cancer 2:232-260(2011) [PubMed] [Europe PMC] [Abstract]

"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]

"An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]

"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 375:554-560(1995) [PubMed] [Europe PMC] [Abstract]

"Ras/Rap effector specificity determined by charge reversal."
Nat. Struct. Biol. 3:723-729(1996) [PubMed] [Europe PMC] [Abstract]

"Solution structure of the Ras-binding domain of c-Raf-1 and identification of its Ras interaction surface."
Biochemistry 34:6911-6918(1995) [PubMed] [Europe PMC] [Abstract]

"The solution structure of the Raf-1 cysteine-rich domain: a novel ras and phospholipid binding site."
Proc. Natl. Acad. Sci. U.S.A. 93:8312-8317(1996) [PubMed] [Europe PMC] [Abstract]

"Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy."
Nat. Genet. 39:1007-1012(2007) [PubMed] [Europe PMC] [Abstract]

"Germline gain-of-function mutations in RAF1 cause Noonan syndrome."
Nat. Genet. 39:1013-1017(2007) [PubMed] [Europe PMC] [Abstract]

"Patterns of somatic mutation in human cancer genomes."
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]

"Noonan syndrome associated with both a new Jnk-activating familial SOS1 and a de novo RAF1 mutations."
Am. J. Med. Genet. A 152:2176-2184(2010) [PubMed] [Europe PMC] [Abstract]

"RAF1 mutations in childhood-onset dilated cardiomyopathy."
Nat. Genet. 46:635-639(2014) [PubMed] [Europe PMC] [Abstract]