Genomes and Genes
Gene Symbol: Raf1
Description: v-raf-leukemia viral oncogene 1
Alias: 6430402F14Rik, AA990557, BB129353, Craf1, D830050J10Rik, Raf-1, c-Raf, cRaf, v-Raf, RAF proto-oncogene serine/threonine-protein kinase, Craf1 transforming, murine sarcoma 3611 oncogene 1, proto-oncogene c-RAF
- Kolch W, Heidecker G, Lloyd P, Rapp U. Raf-1 protein kinase is required for growth of induced NIH/3T3 cells. Nature. 1991;349:426-8 pubmed..We conclude that raf functions as an essential signal transducer downstream of serum growth factor receptors, protein kinase C and ras. ..
- Kerkhoff E, Fedorov L, Siefken R, Walter A, Papadopoulos T, Rapp U. Lung-targeted expression of the c-Raf-1 kinase in transgenic mice exposes a novel oncogenic character of the wild-type protein. Cell Growth Differ. 2000;11:185-90 pubmed..Our studies show that the c-Raf-1 expression level is a critical parameter in tumor development and should be analyzed in more detail to evaluate its potential in the induction of cancer. ..
- Dumaz N, Hayward R, Martin J, Ogilvie L, Hedley D, Curtin J, et al. In melanoma, RAS mutations are accompanied by switching signaling from BRAF to CRAF and disrupted cyclic AMP signaling. Cancer Res. 2006;66:9483-91 pubmed..We show that cAMP suppresses CRAF activity in melanocytes and that this is essential to suppress the oncogenic potential of CRAF in these cells...
- Ehrenreiter K, Kern F, Velamoor V, Meissl K, Galabova Kovacs G, Sibilia M, et al. Raf-1 addiction in Ras-induced skin carcinogenesis. Cancer Cell. 2009;16:149-60 pubmed publisher..These data link the Raf-1:Rok-alpha complex to STAT3/Myc activation and delineate a pathway crucial for cell fate decision in Ras-induced tumorigenesis. ..
- Niault T, Sobczak I, Meissl K, Weitsman G, Piazzolla D, Maurer G, et al. From autoinhibition to inhibition in trans: the Raf-1 regulatory domain inhibits Rok-alpha kinase activity. J Cell Biol. 2009;187:335-42 pubmed publisher..Downstream of Ras and Rho, the Raf-1-Rok-alpha interaction represents a novel paradigm of pathway cross talk that contributes to tumorigenesis and cell motility. ..
- Mikula M, Schreiber M, Husak Z, Kucerova L, Ruth J, Wieser R, et al. Embryonic lethality and fetal liver apoptosis in mice lacking the c-raf-1 gene. EMBO J. 2001;20:1952-62 pubmed..These results indicate that the essential function of Raf-1 is to counteract apoptosis rather than to promote proliferation, and that effectors distinct from the MEK/ERK cascade must mediate the anti-apoptotic function of Raf-1. ..
- Alejandro E, Johnson J. Inhibition of Raf-1 alters multiple downstream pathways to induce pancreatic beta-cell apoptosis. J Biol Chem. 2008;283:2407-17 pubmed..These studies identify Raf-1 as a critical anti-apoptotic kinase in pancreatic beta-cells and contribute to our understanding of survival signaling in this cell type. ..
- Ehrenreiter K, Piazzolla D, Velamoor V, Sobczak I, Small J, Takeda J, et al. Raf-1 regulates Rho signaling and cell migration. J Cell Biol. 2005;168:955-64 pubmed..Thus, Raf-1 plays an essential, kinase-independent function as a spatial regulator of Rho downstream signaling during migration. ..
- Kolbus A, Pilat S, Husak Z, Deiner E, Stengl G, Beug H, et al. Raf-1 antagonizes erythroid differentiation by restraining caspase activation. J Exp Med. 2002;196:1347-53 pubmed..These results reveal an essential function of Raf-1 in erythropoiesis and demonstrate that the ability of Raf-1 to restrict caspase activation is biologically relevant in a context distinct from apoptosis. ..
- Huser M, Luckett J, Chiloeches A, Mercer K, Iwobi M, Giblett S, et al. MEK kinase activity is not necessary for Raf-1 function. EMBO J. 2001;20:1940-51 pubmed..These results strongly argue that MEK kinase activity of Raf-1 is not essential for normal mouse development and that Raf-1 plays a key role in preventing apoptosis. ..
- Wojnowski L, Stancato L, Larner A, Rapp U, Zimmer A. Overlapping and specific functions of Braf and Craf-1 proto-oncogenes during mouse embryogenesis. Mech Dev. 2000;91:97-104 pubmed..Here we describe the phenotype of mouse mutants with different combinations of mutant Craf-1 and Braf alleles...
- Hughes P, Renshaw M, Pfaff M, Forsyth J, Keivens V, Schwartz M, et al. Suppression of integrin activation: a novel function of a Ras/Raf-initiated MAP kinase pathway. Cell. 1997;88:521-30 pubmed..Thus, regulation of integrin affinity state is a novel, transcription-independent function of a Ras-linked MAP kinase pathway that may mediate a negative feedback loop in integrin function. ..
- Beith J, Alejandro E, Johnson J. Insulin stimulates primary beta-cell proliferation via Raf-1 kinase. Endocrinology. 2008;149:2251-60 pubmed publisher..These findings have significant implications for the understanding of the regulation of beta-cell mass in both the hyperinsulinemic and insulin-deficient states that occur in the various forms of diabetes. ..
- Harris I, Zhang S, Treskov I, Kovacs A, Weinheimer C, Muslin A. Raf-1 kinase is required for cardiac hypertrophy and cardiomyocyte survival in response to pressure overload. Circulation. 2004;110:718-23 pubmed..These results establish that Raf-1 kinase activity is essential for cardiac hypertrophy and cardiomyocyte survival in response to pressure overload. ..
- Valluet A, Druillennec S, Barbotin C, Dorard C, Monsoro Burq A, Larcher M, et al. B-Raf and C-Raf are required for melanocyte stem cell self-maintenance. Cell Rep. 2012;2:774-80 pubmed publisher..Therefore, Raf signaling is dispensable for early melanocyte lineage development, but necessary for MSC maintenance. ..
- Lin J, Makris A, McMahon C, Bear S, Patriotis C, Prasad V, et al. The ankyrin repeat-containing adaptor protein Tvl-1 is a novel substrate and regulator of Raf-1. J Biol Chem. 1999;274:14706-15 pubmed..These data suggest that Tvl-1 is both a target as well as a regulator of Raf-1. The human homologue of Tvl-1 maps to chromosome 19p12, upstream of MEF2B with the two genes in a head to head arrangement. ..
- Guzman C, Solman M, Ligabue A, Blaževitš O, Andrade D, Reymond L, et al. The efficacy of Raf kinase recruitment to the GTPase H-ras depends on H-ras membrane conformer-specific nanoclustering. J Biol Chem. 2014;289:9519-33 pubmed publisher..We postulate that cancer- and developmental disease-linked mutations that are associated with the Ras membrane conformation may exhibit so far unrecognized Ras nanoclustering and therefore signaling alterations. ..
- Storm S, Cleveland J, Rapp U. Expression of raf family proto-oncogenes in normal mouse tissues. Oncogene. 1990;5:345-51 pubmed..We found no effect of gender on raf expression in non-sex related tissues, nor does tissue germline of origin correlate with levels of expression for any of the three genes. ..
- Patel A, Rochelle J, Jones J, Sumegi J, Uhl G, Seldin M, et al. Mapping of the taurine transporter gene to mouse chromosome 6 and to the short arm of human chromosome 3. Genomics. 1995;25:314-7 pubmed..These data extend a conserved linkage group on mouse chromosome 6 and human chromosome 3p. Deletion of TAUT might contribute to some phenotypic features of the 3p- syndrome. ..
- Santos J, Pellicer A. Novel RFLPs at protooncogene and cancer-related gene loci on mouse chromosomes. Cytogenet Cell Genet. 1993;62:217-9 pubmedDNA probes for the NRAS, HRAS, KRAS2, LCK, RAF1, MET, MYCL1, MYCN, MYB, ERBB2, FOS, CSF1R, and SRC protooncogene loci; the retinoblastoma gene locus (RB1); the tumor virus integration sites INT2, PVT1, and MLV12; and the locus of the ..
- Dai P, Xiong W, Mei L. Erbin inhibits RAF activation by disrupting the sur-8-Ras-Raf complex. J Biol Chem. 2006;281:927-33 pubmed..These results demonstrate a regulatory role of Erbin in the Ras-Raf-MEK pathway, suggesting that Erbin may inhibit ERK activation by disrupting the Sur-8-Ras/Raf interaction. ..
- Rohrbeck A, Borlak J. Cancer genomics identifies regulatory gene networks associated with the transition from dysplasia to advanced lung adenocarcinomas induced by c-Raf-1. PLoS ONE. 2009;4:e7315 pubmed publisher..This study provides insight into molecular pertubations allowing dysplasia to progress further to adenocarcinoma induced by exaggerted c-Raf kinase activity. ..
- Doma E, Rupp C, Varga A, Kern F, Riegler B, Baccarini M. Skin tumorigenesis stimulated by Raf inhibitors relies upon Raf functions that are dependent and independent of ERK. Cancer Res. 2013;73:6926-37 pubmed publisher..Taken together, our findings suggest that combination therapies targeting ERK-dependent and -independent functions of Raf may be more efficient but also safer for cancer treatment. ..
- Lopez Ilasaca M, Bernabe Ortiz J, Na S, Dzau V, Xavier R. Bioluminescence resonance energy transfer identify scaffold protein CNK1 interactions in intact cells. FEBS Lett. 2005;579:648-54 pubmed..These results identify hCNK1 as a specific partner of Rho proteins both in vitro and in vivo and suggest a role of hCNK1 in the signal transduction of Rho proteins. ..
- Swaroop A, Yang Feng T, Liu W, Gieser L, Barrow L, Chen K, et al. Molecular characterization of a novel human gene, SEC13R, related to the yeast secretory pathway gene SEC13, and mapping to a conserved linkage group on human chromosome 3p24-p25 and mouse chromosome 6. Hum Mol Genet. 1994;3:1281-6 pubmed..The mouse Sec13r gene was mapped to the conserved linkage group on chromosome 6 that corresponds to human chromosome 3p24-p25. ..
- Feng L, Xie X, Ding Q, Luo X, He J, Fan F, et al. Spatial regulation of Raf kinase signaling by RKTG. Proc Natl Acad Sci U S A. 2007;104:14348-53 pubmed..Collectively, our results reveal a paradigm of spatial regulation of Raf kinase by RKTG via sequestrating Raf-1 to the Golgi apparatus and thereby inhibiting the ERK signaling pathway. ..
- Wang H, Gambosova K, Cooper Z, Holloway M, Kassai A, Izquierdo D, et al. EGF regulates survivin stability through the Raf-1/ERK pathway in insulin-secreting pancreatic ?-cells. BMC Mol Biol. 2010;11:66 pubmed publisher..This mechanism may be important for regulating ?-cell expansion after birth. ..
- Aldaz C, Yeung R, Latif F, Lerman M, Xiao G, Trono D, et al. Colocalization of the rat homolog of the von Hippel Lindau (Vhl) gene and the plasma membrane Ca++ transporting ATPase isoform 2 (Atp2b2) gene to rat chromosome bands 4q41.3-->42.1. Cytogenet Cell Genet. 1995;71:253-6 pubmed..These two genes together with Raf1 appear to be members of a large syntenic gene cluster that maps to human chromosome bands 3p25-->p26, mouse ..
- Dumaz N, Marais R. Protein kinase A blocks Raf-1 activity by stimulating 14-3-3 binding and blocking Raf-1 interaction with Ras. J Biol Chem. 2003;278:29819-23 pubmed..These studies suggest that Raf-1 and cAMP form a signaling complex in cells. Upon activation of PKA, Raf-1 is phosphorylated and 14-3-3 binds, blocking Raf-1 recruitment to the plasma membrane and preventing its activation. ..
- Yamauchi N, Kiessling A, Cooper G. The Ras/Raf signaling pathway is required for progression of mouse embryos through the two-cell stage. Mol Cell Biol. 1994;14:6655-62 pubmed
- Giblett S, Lloyd D, Light Y, Marais R, Pritchard C. Expression of kinase suppressor of Ras in the normal adult and embryonic mouse. Cell Growth Differ. 2002;13:307-13 pubmed..5 embryo and at high levels in the neuroepithelium of the E10.5 embryo. At this embryonic stage, expression is also detected at lower levels in the limb and tail buds as well as in the myocardium. ..
- Li X, Stevens P, Liu J, Yang H, Wang W, Wang C, et al. PHLPP is a negative regulator of RAF1, which reduces colorectal cancer cell motility and prevents tumor progression in mice. Gastroenterology. 2014;146:1301-12.e1-10 pubmed publisher..We used co-immunoprecipitation assays to identify substrates of PHLPP1 and PHLPP2. We studied phosphorylation of RAF1 in CRC cells that express exogenous PHLPP1 or PHLPP2, or lentiviral-based small hairpin RNAs against their ..
- Okuda K. A new model to evaluate Raf signaling in hematopoietic cells. Int J Oncol. 2013;43:903-10 pubmed publisher..This EPOR/CR3 system may serve as a useful model to evaluate the unknown Raf kinase pathway and the effects of signal transduction inhibitors for Raf as a target. ..
- Cleveland J, Troppmair J, Packham G, Askew D, Lloyd P, Gonzalez Garcia M, et al. v-raf suppresses apoptosis and promotes growth of interleukin-3-dependent myeloid cells. Oncogene. 1994;9:2217-26 pubmed..Therefore, transformation of myeloid cells by v-raf involves signaling pathways which promote both cell cycle progression and cell survival. ..
- Vojtek A, Hollenberg S, Cooper J. Mammalian Ras interacts directly with the serine/threonine kinase Raf. Cell. 1993;74:205-14 pubmed..Using purified bacterially expressed fusion proteins, we show, furthermore, that Ras and the N-terminal region of Raf associate directly in vitro and that this interaction is dependent on GTP bound to Ras. ..
- Miltenberger R, Cortner J, Farnham P. An inhibitory Raf-1 mutant suppresses expression of a subset of v-raf-activated genes. J Biol Chem. 1993;268:15674-80 pubmed..We conclude that Raf-1 is both sufficient and necessary to activate a subset of early and late growth response genes. ..
- Dhillon A, Meikle S, Peyssonnaux C, Grindlay J, Kaiser C, Steen H, et al. A Raf-1 mutant that dissociates MEK/extracellular signal-regulated kinase activation from malignant transformation and differentiation but not proliferation. Mol Cell Biol. 2003;23:1983-93 pubmed..The results further suggest that RafS259 mutants inhibit signaling pathways required to promote these biological processes. ..
- Kebache S, Ash J, Annis M, Hagan J, Huber M, Hassard J, et al. Grb10 and active Raf-1 kinase promote Bad-dependent cell survival. J Biol Chem. 2007;282:21873-83 pubmed..Because total Raf-1, ERK, and Akt kinase activities are not impaired in the absence of Grb10, we propose that this adapter protein creates a subpopulation of Raf-1 with specific anti-apoptotic activity. ..
- Malik N, Gilroy D, Kabouridis P. Regulation of growth and survival of activated T cells by cell-transducing inhibitors of Ras. FEBS Lett. 2009;583:61-9 pubmed publisher..Our data reveal a pro-survival role for Ras in activated primary T cells and describe a new methodology for regulating its activity. ..
- Edelblum K, Goettel J, Koyama T, McElroy S, Yan F, Polk D. TNFR1 promotes tumor necrosis factor-mediated mouse colon epithelial cell survival through RAF activation of NF-kappaB. J Biol Chem. 2008;283:29485-94 pubmed publisher..Thus, further understanding of colon epithelial cell-specific TNFR signaling may result in the identification of new targets for inflammatory bowel disease treatment and define novel mediators of colitis-associated cancer. ..
- Noble C, Mercer K, Hussain J, Carragher L, Giblett S, Hayward R, et al. CRAF autophosphorylation of serine 621 is required to prevent its proteasome-mediated degradation. Mol Cell. 2008;31:862-72 pubmed publisherThe CRAF protein kinase regulates proliferative, differentiation, and survival signals from activated RAS proteins to downstream effectors, most often by inducing MEK/ERK activation...
- Lim J, Kim H, Jeun S, Kang S, Lee K. Merlin inhibits growth hormone-regulated Raf-ERKs pathways by binding to Grb2 protein. Biochem Biophys Res Commun. 2006;340:1151-7 pubmed
- Bucan M, Yang Feng T, Colberg Poley A, Wolgemuth D, Guenet J, Francke U, et al. Genetic and cytogenetic localisation of the homeo box containing genes on mouse chromosome 6 and human chromosome 7. EMBO J. 1986;5:2899-905 pubmed..Here we localise human sequences hybridising to the mouse m6 probes to the short arm of chromosome 7, breaking the region of synteny. ..
- Elliott R, Sparkes R, Mohandas T, Grant S, McGinnis J. Localization of the rhodopsin gene to the distal half of mouse chromosome 6. Genomics. 1990;6:635-44 pubmed..4 map units proximal to the locus for the proto-oncogene Kras-2. Linkage to Raf-1 was confirmed using four sets of recombinant inbred strains. The two loci RAF1 and RHO are also syntenic on human chromosome 3, but on opposite arms.
- Liu E, Raimann A, Chae B, Martins J, Baccarini M, Demay M. c-Raf promotes angiogenesis during normal growth plate maturation. Development. 2016;143:348-55 pubmed publisher..Because c-Raf (Raf1) phosphorylation is increased by extracellular phosphate and c-Raf is the predominant isoform expressed in ..
- Liao J, Hwang S, Li H, Yang Y, Yang J, Wecksler A, et al. Inhibition of mutant KrasG12D-initiated murine pancreatic carcinoma growth by a dual c-Raf and soluble epoxide hydrolase inhibitor t-CUPM. Cancer Lett. 2016;371:187-93 pubmed publisher..Inhibition of mutant Kras-transmitted phosphorylations of cRAF/MEK/ERK was demonstrated in these pancreatic cancer cells using Western blot assay and immunohistochemical approach...
- Jerić I, Maurer G, Cavallo A, Raguz J, Desideri E, Tarkowski B, et al. A cell-autonomous tumour suppressor role of RAF1 in hepatocarcinogenesis. Nat Commun. 2016;7:13781 pubmed publisher..Unexpectedly, RAF1 expression is reduced in human HCC samples...
- Yin J, Platt M, Tian X, Wu X, Backx P, Simpson J, et al. Cellular interplay via cytokine hierarchy causes pathological cardiac hypertrophy in RAF1-mutant Noonan syndrome. Nat Commun. 2017;8:15518 pubmed publisher..NS patients with kinase-activating RAF1 alleles typically develop pathological left ventricular hypertrophy (LVH), which is reproduced in Raf1L613V/+Tansey M, Chu G, Merlie J. ARIA/HRG regulates AChR epsilon subunit gene expression at the neuromuscular synapse via activation of phosphatidylinositol 3-kinase and Ras/MAPK pathway. J Cell Biol. 1996;134:465-76 pubmed..Thus, synaptic induction of AChR genes requires activation of both Ras/MAPK and PI3K signal transduction pathways. ..Seldin M, Rochelle J, Tomlinson M, Wright M. Mapping of the genes for four members of the transmembrane 4 superfamily: mouse Cd9, Cd63, Cd81, and Cd82. Immunogenetics. 1995;42:422-5 pubmedPacker L, Rana S, Hayward R, O Hare T, Eide C, Rebocho A, et al. Nilotinib and MEK inhibitors induce synthetic lethality through paradoxical activation of RAF in drug-resistant chronic myeloid leukemia. Cancer Cell. 2011;20:715-27 pubmed publisher..and dasatinib possess weak off-target activity against RAF and, therefore, drive paradoxical activation of BRAF and CRAF in a RAS-dependent manner...Napoli I, Noon L, Ribeiro S, Kerai A, Parrinello S, Rosenberg L, et al. A central role for the ERK-signaling pathway in controlling Schwann cell plasticity and peripheral nerve regeneration in vivo. Neuron. 2012;73:729-42 pubmed publisher..This reversible in vivo model identifies a central role for ERK signaling in Schwann cells in orchestrating nerve repair and is a powerful system for studying peripheral neuropathies and cancer. ..Wadewitz A, Winer M, Wolgemuth D. Developmental and cell lineage specificity of raf family gene expression in mouse testis. Oncogene. 1993;8:1055-62 pubmed..These studies indicate that each raf gene exhibits a characteristic, limited pattern of expression and suggests that the different forms may play a unique regulatory role in androgen production and/or spermatogenesis. ..Mercer K, Giblett S, Oakden A, Brown J, Marais R, Pritchard C. A-Raf and Raf-1 work together to influence transient ERK phosphorylation and Gl/S cell cycle progression. Oncogene. 2005;24:5207-17 pubmed..Levels of sustained ERK phosphorylation are not significantly altered. Thus, Raf-1 and A-Raf have a combined role in controlling physiological transient ERK activation and in maintenance of cell cycle progression at its usual rate. ..Provot S, Nachtrab G, Paruch J, Chen A, Silva A, Kronenberg H. A-raf and B-raf are dispensable for normal endochondral bone development, and parathyroid hormone-related peptide suppresses extracellular signal-regulated kinase activation in hypertrophic chondrocytes. Mol Cell Biol. 2008;28:344-57 pubmedTailor S, Martin DeLeon P. Localization of the raf-1 protooncogene on chromosome 6 of the mouse. Cancer Genet Cytogenet. 1989;40:89-94 pubmed..The localization of this protooncogene may be relevant to the correlation of chromosome breakpoints in neoplastic disease. ..Yao Z, Fanslow W, Seldin M, Rousseau A, Painter S, Comeau M, et al. Herpesvirus Saimiri encodes a new cytokine, IL-17, which binds to a novel cytokine receptor. Immunity. 1995;3:811-21 pubmed..These results define CTLA8 and HVS13 as novel cytokines that bind to a novel cytokine receptor. We propose to call these molecules IL-17, vIL-17, and IL-17R, respectively. ..Gerits N, Kostenko S, Moens U. In vivo functions of mitogen-activated protein kinases: conclusions from knock-in and knock-out mice. Transgenic Res. 2007;16:281-314 pubmed..Moreover, examples of the application of MAP kinase transgenic mice for validating therapeutic properties of specific MAP kinase inhibitors, and for investigating the role of MAP kinase in pathogen-host interactions will be discussed. ..Chen C, Lewis R, White M. IMP modulates KSR1-dependent multivalent complex formation to specify ERK1/2 pathway activation and response thresholds. J Biol Chem. 2008;283:12789-96 pubmed publisher..MEK complexes that are required for c-Raf kinase activation and functional coupling of active kinases to downstream substrates. This property is engaged by IMP for modulation of signal amplitude. ..An H, Maeng O, Kang K, Lee J, Kim Y, Paik S, et al. Activation of Ras up-regulates pro-apoptotic BNIP3 in nitric oxide-induced cell death. J Biol Chem. 2006;281:33939-48 pubmed..These results suggest that NO-induced death of macrophages is mediated, at least in part, by BNIP3 induction. ..Papaioannou G, Petit E, Liu E, Baccarini M, Pritchard C, Demay M. Raf Kinases Are Essential for Phosphate Induction of ERK1/2 Phosphorylation in Hypertrophic Chondrocytes and Normal Endochondral Bone Development. J Biol Chem. 2017;292:3164-3171 pubmed publisher..These data further demonstrated that Raf kinases are required for phosphate-induced ERK1/2 phosphorylation in cultured hypertrophic chondrocytes and perform essential, but partially redundant roles in growth plate maturation. ..Wojnowski L, Zimmer A, Beck T, Hahn H, Bernal R, Rapp U, et al. Endothelial apoptosis in Braf-deficient mice. Nat Genet. 1997;16:293-7 pubmed..role for Raf as a suppressor of programmed cell death has been suggested by the recent finding that Craf1 interacts with members of the Bcl-2 family at mitochondrial membranes. However, genetic studies of C...Arcaroli J, Yang K, Yum H, Kupfner J, Pitts T, Park J, et al. Effects of catecholamines on kinase activation in lung neutrophils after hemorrhage or endotoxemia. J Leukoc Biol. 2002;72:571-9 pubmedVoss G, Jockusch H. Genetic mapping of members of the polyubiquitin gene subfamily coding for UbB. Mamm Genome. 1996;7:169 pubmedWu X, Yin J, Simpson J, Kim K, Gu S, Hong J, et al. Increased BRAF heterodimerization is the common pathogenic mechanism for noonan syndrome-associated RAF1 mutants. Mol Cell Biol. 2012;32:3872-90 pubmed publisher..mitogen-activated protein kinase (MAPK) pathway, including both kinase-activating and kinase-impaired alleles of RAF1 (?3 to 5%), which encodes a serine-threonine kinase for MEK1/2...Lorenz K, Lohse M, Quitterer U. Protein kinase C switches the Raf kinase inhibitor from Raf-1 to GRK-2. Nature. 2003;426:574-9 pubmed..A physiological role for this mechanism is shown in cardiomyocytes in which the downregulation of RKIP restrains beta-adrenergic signalling and contractile activity. ..Lange Carter C, Pleiman C, Gardner A, Blumer K, Johnson G. A divergence in the MAP kinase regulatory network defined by MEK kinase and Raf. Science. 1993;260:315-9 pubmed..Thus, MEKK and Raf converge at MEK in the protein kinase network mediating the activation of MAPKs by hormones, growth factors, and neurotransmitters. ..Bidzhekov K, Hautmann M, Semisch M, Weber C, Engelmann B, Hatzopoulos A. Rafs constitute a nodal point in the regulation of embryonic endothelial progenitor cell growth and differentiation. J Cell Mol Med. 2007;11:1395-407 pubmed publisher..Thus, gain- and loss-of-function experiments point to distinct roles of B-Raf and C-Raf in regulating growth and differentiation of endothelial progenitor cells, which may harbour therapeutic implications. ..McCarthy S, Samuels M, Pritchard C, Abraham J, McMahon M. Rapid induction of heparin-binding epidermal growth factor/diphtheria toxin receptor expression by Raf and Ras oncogenes. Genes Dev. 1995;9:1953-64 pubmedGalabova Kovacs G, Kolbus A, Matzen D, Meissl K, Piazzolla D, Rubiolo C, et al. ERK and beyond: insights from B-Raf and Raf-1 conditional knockouts. Cell Cycle. 2006;5:1514-8 pubmed..Here, we discuss some of the surprises yielded by the analysis of the role of B-Raf and Raf-1 and of their downstream effectors. ..Klinken S, Hartley J, Fredrickson T, Rapp U, Morse H. Susceptibility to raf and raf/myc retroviruses is governed by different genetic loci. J Virol. 1989;63:2411-4 pubmed..From these data and the susceptibility of C x B recombinant inbred strains, it appears that very few genes (perhaps even a single gene) may govern susceptibility to raf/myc lymphomas and that resistance is the dominant trait...Rodríguez Muñoz M, de la Torre Madrid E, Sánchez Blázquez P, Garzón J. NO-released zinc supports the simultaneous binding of Raf-1 and PKC? cysteine-rich domains to HINT1 protein at the mu-opioid receptor. Antioxid Redox Signal. 2011;14:2413-25 pubmed publisher..This study reveals new aspects of ERK1/2 regulation by the MOR without requiring the transactivation of a receptor tyrosine kinase. ..Mock B, Connelly M, McBride O, Kozak C, Marcu K. Plasmacytoma-associated neuronal glycoprotein, Pang, maps to mouse chromosome 6 and human chromosome 3. Genomics. 1996;34:226-8 pubmed..Southern blot analysis of human-rodent somatic cell hybrids together with predictions from the mouse map location indicate that human PANG is located at 3p26. ..Jones P, Savory R, Barratt P, Bell A, Gray T, Jenkins N, et al. Chromosomal localisation, inducibility, tissue-specific expression and strain differences in three murine peroxisome-proliferator-activated-receptor genes. Eur J Biochem. 1995;233:219-26 pubmed..Polymorphism in the size of PPAR alpha RNA from Swiss-Webster mice was detected, and shown to be due to a 2-bp mutation in the 3' non-coding region of PPAR alpha in Swiss Webster mice. ..Wojnowski L, Stancato L, Zimmer A, Hahn H, Beck T, Larner A, et al. Craf-1 protein kinase is essential for mouse development. Mech Dev. 1998;76:141-9 pubmed..We report here that Craf-1 is essential for mouse development, as its mutation results in embryonic lethality...Ingram D, Hiatt K, King A, Fisher L, Shivakumar R, Derstine C, et al. Hyperactivation of p21(ras) and the hematopoietic-specific Rho GTPase, Rac2, cooperate to alter the proliferation of neurofibromin-deficient mast cells in vivo and in vitro. J Exp Med. 2001;194:57-69 pubmedWang K, Yin X, Copeland N, Gilbert D, Jenkins N, Keck C, et al. BID, a proapoptotic BCL-2 family member, is localized to mouse chromosome 6 and human chromosome 22q11. Genomics. 1998;53:235-8 pubmed..Fluorescence in situ hybridization analysis localized human BID to a syntenic human region, chromosome 22q11, close to the BCR-1 gene. ..Lee M, Kim J, Anderson W. Src tyrosine kinase inhibitor PP2 markedly enhances Ras-independent activation of Raf-1 protein kinase by phorbol myristate acetate and H2O2. J Biol Chem. 2004;279:48692-701 pubmed..This PP2 effect resulted in significant and sustained Ras-independent activation of Raf-1 by PMA and H2O2. ..Adamson M, Dennis C, Delaney S, Christiansen J, Monkley S, Kozak C, et al. Isolation and genetic mapping of two novel members of the murine Wnt gene family, Wnt11 and Wnt12, and the mapping of Wnt5a and Wnt7a. Genomics. 1994;24:9-13 pubmed..Interspecific crosses were used to demonstrate close linkage between Wnt12 and Wnt1 on Chromosome (Chr) 15. Wnt7a was mapped to mouse Chr 6, Wnt5a to the centromeric region of Chr 14, and Wnt11 to Chr7. ..Gentschev I, Fensterle J, Schmidt A, Potapenko T, Troppmair J, Goebel W, et al. Use of a recombinant Salmonella enterica serovar Typhimurium strain expressing C-Raf for protection against C-Raf induced lung adenoma in mice. BMC Cancer. 2005;5:15 pubmed..The combination of the C-Raf antigen, hemolysin secretion system and Salmonella enterica serovar Typhimurium could form the basis for a new generation of live bacterial vaccines for the treatment of Raf dependent human malignancies. ..Tarutani M, Imai Y, Yasuda K, Tsutsui H, Nakanishi K, Yamanishi K. Neutrophil-dominant psoriasis-like skin inflammation induced by epidermal-specific expression of Raf in mice. J Dermatol Sci. 2010;58:28-35 pubmed publisher..Activation of the Raf signaling pathway is involved in the epidermal hyperplasia and the neutrophil-dominant cutaneous inflammatory reactions which are characteristics of psoriasis. ..Roring M, Herr R, Fiala G, Heilmann K, Braun S, Eisenhardt A, et al. Distinct requirement for an intact dimer interface in wild-type, V600E and kinase-dead B-Raf signalling. EMBO J. 2012;31:2629-47 pubmed publisher..Our data further implicate the Raf DIF as a potential target against Ras-driven Raf-mediated (paradoxical) ERK activation. ..Moore K, D Amore Bruno M, Korfhagen T, Glasser S, Whitsett J, Jenkins N, et al. Chromosomal localization of three pulmonary surfactant protein genes in the mouse. Genomics. 1992;12:388-93 pubmed..The mouse map locations determined in this study for the Sftp genes are consistent with the locations of these genes on the human genetic map and the syntenic relationships between the human and the mouse genomes. ..Ray J, Harbison M, McClain R, Goodman J. Alterations in the methylation status and expression of the raf oncogene in phenobarbital-induced and spontaneous B6C3F1 mouse liver tumors. Mol Carcinog. 1994;9:155-66 pubmedLi A, Tian X, Zhang X, Huang S, Ma Y, Wu D, et al. Human polycystin-2 transgene dose-dependently rescues ADPKD phenotypes in Pkd2 mutant mice. Am J Pathol. 2015;185:2843-60 pubmed publisher..The finding that the functional restoration of human PC2 significantly rescued ADPKD phenotypes in a dose-dependent manner suggests that increasing PC2 activity may be beneficial in some forms of ADPKD. ..Kamata T, Pritchard C, Leavitt A. Raf-1 is not required for megakaryocytopoiesis or TPO-induced ERK phosphorylation. Blood. 2004;103:2568-70 pubmed..These unexpected findings demonstrate that Raf-1 is dispensable for megakaryocytopoiesis, and for thrombopoietin-induced ERK1/2 activation in primary megakaryocyte-lineage cells. ..