Gene Symbol: Rapgef1
Description: Rap guanine nucleotide exchange factor (GEF) 1
Alias: 4932418O06Rik, C3G, Grf2, rap guanine nucleotide exchange factor 1, guanine nucleotide releasing factor 2
Species: mouse
Products:     Rapgef1

Top Publications

  1. Wei P, Satoh T, Edamatsu H, Aiba A, Setsu T, Terashima T, et al. Defective vascular morphogenesis and mid-gestation embryonic death in mice lacking RA-GEF-1. Biochem Biophys Res Commun. 2007;363:106-12 pubmed
    ..Furthermore, RA-GEF-1(-/-) embryos proper show severe defects in the formation of major blood vessels. These results suggest that deficient Rap1 signaling may lead to defective vascular morphogenesis in the yolk sac and embryos proper. ..
  2. Weissman J, Ma J, Essex A, Gao Y, Burstein E. G-protein-coupled receptor-mediated activation of rap GTPases: characterization of a novel Galphai regulated pathway. Oncogene. 2004;23:241-9 pubmed
    ..Responses to 5HT1E, but not D1, were sensitive to inhibition by a dominant-negative C3G fragment, by the Src-like kinase inhibitors PP1 and PP2, and by a dominant-negative mutant of Src...
  3. Shah B, Lutter D, Bochenek M, Kato K, Tsytsyura Y, Glyvuk N, et al. C3G/Rapgef1 Is Required in Multipolar Neurons for the Transition to a Bipolar Morphology during Cortical Development. PLoS ONE. 2016;11:e0154174 pubmed publisher
    ..Here we show that the Rap1 guanine nucleotide exchange factor (GEF) C3G (encoded by the Rapgef1 gene) is a crucial regulator of the MTB transition in vivo by conditionally inactivating the Rapgef1 gene in the ..
  4. Amsen D, Kruisbeek A, Bos J, Reedquist K. Activation of the Ras-related GTPase Rap1 by thymocyte TCR engagement and during selection. Eur J Immunol. 2000;30:2832-41 pubmed
    ..Rap1 (the proto-oncogene product Cbl, Crk family adaptor proteins, and the Rap1 guanine nucleotide exchange factor C3G) are expressed at equivalent levels in both double-negative and double-positive murine thymocytes...
  5. Schmitt J, Stork P. PKA phosphorylation of Src mediates cAMP's inhibition of cell growth via Rap1. Mol Cell. 2002;9:85-94 pubmed
    ..We demonstrate here that PKA's activation of Rap1 was mediated by the Rap1 guanine nucleotide exchange factor C3G, the adaptor Crk-L, the scaffold protein Cbl, and the tyrosine kinase Src...
  6. Shi S, Noda M, Kitayama H. Rap1 mutants with increased affinity for the guanine-nucleotide exchange factor C3G. Oncogene. 2004;23:8711-9 pubmed
    ..Rap1 (Rap1-17N) fails to effectively interfere with the interaction between the wild-type Rap1 and one of its GEFs, C3G, in vitro...
  7. Ferrando I, Chaerkady R, Zhong J, Molina H, Jacob H, Herbst Robinson K, et al. Identification of targets of c-Src tyrosine kinase by chemical complementation and phosphoproteomics. Mol Cell Proteomics. 2012;11:355-69 pubmed publisher
    ..of c-Src provided a tool to dissect the spatiotemporal mechanism of activation of the Rap1 guanine exchange factor, C3G, one of the identified potential c-Src substrates that plays a role in focal adhesion signaling...
  8. Fecchi K, Volonte D, Hezel M, Schmeck K, Galbiati F. Spatial and temporal regulation of GLUT4 translocation by flotillin-1 and caveolin-3 in skeletal muscle cells. FASEB J. 2006;20:705-7 pubmed
    ..of Cbl and CrkII in flotillin-1/GLUT4-containing domains, as well as the activation of the GDP-GTP exchange factor C3G. Disruption of flotillin-1-based domains prevents the activation of C3G, movement of GLUT4 to the sarcolemma, and ..
  9. Schumacher C, Knudsen B, Ohuchi T, Di Fiore P, Glassman R, Hanafusa H. The SH3 domain of Crk binds specifically to a conserved proline-rich motif in Eps15 and Eps15R. J Biol Chem. 1995;270:15341-7 pubmed
    ..Crk might therefore be involved in Eps15-mediated signal transduction through the EGFR. ..

More Information


  1. Moulson C, Martin D, Lugus J, Schaffer J, Lind A, Miner J. Cloning of wrinkle-free, a previously uncharacterized mouse mutation, reveals crucial roles for fatty acid transport protein 4 in skin and hair development. Proc Natl Acad Sci U S A. 2003;100:5274-9 pubmed
    ..However, its function in vivo had not been determined. Our results demonstrate an unexpected yet critical role for FATP4 in skin and hair development and suggest Slc27a4 to be a candidate gene for restrictive dermopathy. ..
  2. Zhang W, Shao Y, Fang D, Huang J, Jeon M, Liu Y. Negative regulation of T cell antigen receptor-mediated Crk-L-C3G signaling and cell adhesion by Cbl-b. J Biol Chem. 2003;278:23978-83 pubmed
    ..Here we examined a regulatory role of Cbl-b in Crk-L-C3G signaling pathway...
  3. Shao Y, Elly C, Liu Y. Negative regulation of Rap1 activation by the Cbl E3 ubiquitin ligase. EMBO Rep. 2003;4:425-31 pubmed
    ..Previous studies have proposed that Cbl is also a positive regulator of CrkL-C3G signalling, which leads to Rap1 activation...
  4. Fernández Medarde A, Esteban L, Nunez A, Porteros A, Tessarollo L, Santos E. Targeted disruption of Ras-Grf2 shows its dispensability for mouse growth and development. Mol Cell Biol. 2002;22:2498-504 pubmed
    The mammalian Grf1 and Grf2 proteins are Ras guanine nucleotide exchange factors (GEFs) sharing a high degree of structural homology, as well as an elevated expression level in central nervous system tissues...
  5. Ballif B, Arnaud L, Arthur W, Guris D, Imamoto A, Cooper J. Activation of a Dab1/CrkL/C3G/Rap1 pathway in Reelin-stimulated neurons. Curr Biol. 2004;14:606-10 pubmed
    ..CrkL also binds C3G, an exchange factor (GEF) for the small GTPase Rap1 that is activated in other systems by tyrosine phosphorylation...
  6. Zhai B, Huo H, Liao K. C3G, a guanine nucleotide exchange factor bound to adapter molecule c-Crk, has two alternative splicing forms. Biochem Biophys Res Commun. 2001;286:61-6 pubmed
    Two types of C3G cDNA were isolated from mouse 3T3-L1 adipocyte cDNA library. A 114-bp sequence in the middle of C3G cDNA is deleted in the short type cDNA...
  7. Heaney C, Kolibaba K, Bhat A, Oda T, Ohno S, Fanning S, et al. Direct binding of CRKL to BCR-ABL is not required for BCR-ABL transformation. Blood. 1997;89:297-306 pubmed
    ..Thus, a direct interaction of CRKL and BCR-ABL is not required for CRKL to become tyrosine phosphorylated by BCR-ABL and suggests that CRKL function may still be required for BCR-ABL function through an indirect interaction. ..
  8. Voss A, Britto J, Dixon M, Sheikh B, Collin C, Tan S, et al. C3G regulates cortical neuron migration, preplate splitting and radial glial cell attachment. Development. 2008;135:2139-49 pubmed publisher
    ..We report here that mouse embryos lacking the Ras family guanine nucleotide exchange factor, C3G (Rapgef1, Grf2), exhibit a cortical neuron migration defect resulting in a failure to split the preplate into marginal ..
  9. Gutierrez Uzquiza A, Arechederra M, Molina I, Baños R, Maia V, Benito M, et al. C3G down-regulates p38 MAPK activity in response to stress by Rap-1 independent mechanisms: involvement in cell death. Cell Signal. 2010;22:533-42 pubmed publisher
    We present here evidences supporting a negative regulation of p38alpha MAPK activity by C3G in MEFs triggered by stress, which can mediate cell death or survival depending on the stimuli...
  10. Yip Y, Thomas T, Voss A, Yip J. Migration of sympathetic preganglionic neurons in the spinal cord of a C3G-deficient mouse suggests that C3G acts in the reelin signaling pathway. J Comp Neurol. 2012;520:3194-202 pubmed
    ..The present study asks whether Rap guanine nucleotide exchange factor (GEF) 1 (C3G/Rap-gef1), a Ras family GEF that binds CrkL, could act downstream in the reelin signaling pathway in control of SPN ..
  11. Gutiérrez Herrero S, Maia V, Gutierrez Berzal J, Calzada N, Sanz M, González Manchón C, et al. C3G transgenic mouse models with specific expression in platelets reveal a new role for C3G in platelet clotting through its GEF activity. Biochim Biophys Acta. 2012;1823:1366-77 pubmed publisher
    We have generated mouse transgenic lineages for C3G (tgC3G) and C3G?Cat (tgC3G?Cat, C3G mutant lacking the GEF domain), where the transgenes are expressed under the control of the megakaryocyte and platelet specific PF4 (platelet factor ..
  12. Gutierrez Berzal J, Castellano E, Martín Encabo S, Gutiérrez Cianca N, Hernandez J, Santos E, et al. Characterization of p87C3G, a novel, truncated C3G isoform that is overexpressed in chronic myeloid leukemia and interacts with Bcr-Abl. Exp Cell Res. 2006;312:938-48 pubmed
    A novel C3G isoform, designated p87C3G, lacking the most amino terminal region of the cognate protein has been found to be overexpressed in two CML cell lines, K562 and Boff 210, both expressing Bcr-Abl p210...
  13. Voss A, Krebs D, Thomas T. C3G regulates the size of the cerebral cortex neural precursor population. EMBO J. 2006;25:3652-63 pubmed
    ..Here, we demonstrate that the Rap1 guanine nucleotide exchange factor, C3G (Grf2, Rapgef1), controls the size of the cerebral precursor population...
  14. Chiang S, Baumann C, Kanzaki M, Thurmond D, Watson R, Neudauer C, et al. Insulin-stimulated GLUT4 translocation requires the CAP-dependent activation of TC10. Nature. 2001;410:944-8 pubmed
    ..Here we show that phosphorylated Cbl recruits the CrkII-C3G complex to lipid rafts, where C3G specifically activates the small GTP-binding protein TC10...
  15. Sasi Kumar K, Ramadhas A, Nayak S, Kaniyappan S, Dayma K, Radha V. C3G (RapGEF1), a regulator of actin dynamics promotes survival and myogenic differentiation of mouse mesenchymal cells. Biochim Biophys Acta. 2015;1853:2629-39 pubmed publisher
    b>RapGEF1 (C3G) is a ubiquitously expressed protein that is essential for mammalian embryonic development. We have shown earlier that C3G regulates cytoskeletal dynamics and is required for neuronal differentiation...
  16. Cheerathodi M, Vincent J, Ballif B. Quantitative comparison of CrkL-SH3 binding proteins from embryonic murine brain and liver: Implications for developmental signaling and the quantification of protein species variants in bottom-up proteomics. J Proteomics. 2015;125:104-11 pubmed publisher
    ..Here we compare the identification and quantification of CrkL-SH3 binding partners between embryonic murine brain and liver. We also uncover and quantify tissue-specific variants in CrkL-SH3 binding proteins. ..
  17. Voss A, Gruss P, Thomas T. The guanine nucleotide exchange factor C3G is necessary for the formation of focal adhesions and vascular maturation. Development. 2003;130:355-67 pubmed
    The Ras signalling pathway has major roles in normal cell function and oncogenesis. C3G is a guanine nucleotide exchange factor for members of the Ras family of GTPases. We generated a mouse strain with a hypomorphic C3G allele...
  18. Ohba Y, Ikuta K, Ogura A, Matsuda J, Mochizuki N, Nagashima K, et al. Requirement for C3G-dependent Rap1 activation for cell adhesion and embryogenesis. EMBO J. 2001;20:3333-41 pubmed
    b>C3G is a guanine nucleotide exchange factor (GEF) for Rap1, and is activated via Crk adaptor protein. To understand the physiological role of C3G, we generated C3G knockout mice. C3G(-/-) homozygous mice died before embryonic day 7.5...
  19. Voss A, Thomas T, Gruss P. Efficiency assessment of the gene trap approach. Dev Dyn. 1998;212:171-80 pubmed
    ..Evidently, gene trapping does not always provide all three of the features mentioned above. In this paper, we discuss the efficiency of gene trapping and ways in which some problems may be overcome. ..
  20. Bithell A, Hsu T, Kandanearatchi A, Landau S, Everall I, Tsuang M, et al. Expression of the Rap1 guanine nucleotide exchange factor, MR-GEF, is altered in individuals with bipolar disorder. PLoS ONE. 2010;5:e10392 pubmed publisher
    ..Since MR-GEF encodes a Rap1 GEF able to activate G-protein signalling, we suggest that changes in MR-GEF expression could potentially influence neurotransmission. ..
  21. Wang S, Aoki M, Nakashima Y, Shinozuka Y, Tanaka H, Taniwaki M, et al. Development of Notch-dependent T-cell leukemia by deregulated Rap1 signaling. Blood. 2008;111:2878-86 pubmed publisher
    ..Herein, we showed that transplantation of HPCs expressing farnesylated C3G (C3G-F), a Rap1 guanine nucleotide exchange factor, resulted in a marked expansion of thymocytes bearing unique ..