RAPGEF1 explained

Rap guanine nucleotide exchange factor 1 is a protein that in humans is encoded by the RAPGEF1 gene.^{[1] [2]}

Function

The protein encoded by this gene is a human guanine nucleotide releasing protein for Ras protein. It belongs to the adaptor-type Src homology (SH)2-containing molecules. Src homology 2 domains are globular protein modules present in a large variety of functionally distinct proteins. They mediate binding events that control the activity and localization of many proteins involved in the transmission of signals from the cell surface to the nucleus. The mRNAs of these proteins are expressed ubiquitously in human adult and fetal tissues. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some variants has not been determined.^[3]

Interactions

RAPGEF1 has been shown to interact with:

• BCAR1,^[4]
• CRK,^[2]
• CRKL^{[5] [6] [7] [8] [9] [10]}
• Grb2,^[11] and
• HCK.^[12]

Further reading

• Pessin JE, Okada S . Insulin and EGF receptors integrate the Ras and Rap signaling pathways . Endocrine Journal . 46 Suppl . S11-6 . Mar 1999 . 12054111 . 10.1507/endocrj.46.suppl_s11 . free .
• Ehrhardt A, Ehrhardt GR, Guo X, Schrader JW . Ras and relatives--job sharing and networking keep an old family together . Experimental Hematology . 30 . 10 . 1089–106 . Oct 2002 . 12384139 . 10.1016/S0301-472X(02)00904-9 . free .
• Knudsen BS, Feller SM, Hanafusa H . Four proline-rich sequences of the guanine-nucleotide exchange factor C3G bind with unique specificity to the first Src homology 3 domain of Crk . The Journal of Biological Chemistry . 269 . 52 . 32781–7 . Dec 1994 . 10.1016/S0021-9258(20)30059-4 . 7806500 . free .
• Gotoh T, Hattori S, Nakamura S, Kitayama H, Noda M, Takai Y, Kaibuchi K, Matsui H, Hatase O, Takahashi H . Identification of Rap1 as a target for the Crk SH3 domain-binding guanine nucleotide-releasing factor C3G . Molecular and Cellular Biology . 15 . 12 . 6746–53 . Dec 1995 . 8524240 . 230928 . 10.1128/mcb.15.12.6746.
• Smit L, van der Horst G, Borst J . Sos, Vav, and C3G participate in B cell receptor-induced signaling pathways and differentially associate with Shc-Grb2, Crk, and Crk-L adaptors . The Journal of Biological Chemistry . 271 . 15 . 8564–9 . Apr 1996 . 8621483 . 10.1074/jbc.271.15.8564 . free .
• Matsuda M, Ota S, Tanimura R, Nakamura H, Matuoka K, Takenawa T, Nagashima K, Kurata T . Interaction between the amino-terminal SH3 domain of CRK and its natural target proteins . The Journal of Biological Chemistry . 271 . 24 . 14468–72 . Jun 1996 . 8662907 . 10.1074/jbc.271.24.14468 . free .
• Uemura N, Salgia R, Li JL, Pisick E, Sattler M, Griffin JD . The BCR/ABL oncogene alters interaction of the adapter proteins CRKL and CRK with cellular proteins . Leukemia . 11 . 3 . 376–85 . Mar 1997 . 9067577 . 10.1038/sj.leu.2400590 . free .
• Husson H, Mograbi B, Schmid-Antomarchi H, Fischer S, Rossi B . CSF-1 stimulation induces the formation of a multiprotein complex including CSF-1 receptor, c-Cbl, PI 3-kinase, Crk-II and Grb2 . Oncogene . 14 . 19 . 2331–8 . May 1997 . 9178909 . 10.1038/sj.onc.1201074 . free .
• Chin H, Saito T, Arai A, Yamamoto K, Kamiyama R, Miyasaka N, Miura O . Erythropoietin and IL-3 induce tyrosine phosphorylation of CrkL and its association with Shc, SHP-2, and Cbl in hematopoietic cells . Biochemical and Biophysical Research Communications . 239 . 2 . 412–7 . Oct 1997 . 9344843 . 10.1006/bbrc.1997.7480 .
• Ahmad S, Alsayed YM, Druker BJ, Platanias LC . The type I interferon receptor mediates tyrosine phosphorylation of the CrkL adaptor protein . The Journal of Biological Chemistry . 272 . 48 . 29991–4 . Nov 1997 . 9374471 . 10.1074/jbc.272.48.29991 . free .
• Guerrero C, Fernandez-Medarde A, Rojas JM, Font de Mora J, Esteban LM, Santos E . Transformation suppressor activity of C3G is independent of its CDC25-homology domain . Oncogene . 16 . 5 . 613–24 . Feb 1998 . 9482107 . 10.1038/sj.onc.1201569 . free .
• Ohashi Y, Tachibana K, Kamiguchi K, Fujita H, Morimoto C . T cell receptor-mediated tyrosine phosphorylation of Cas-L, a 105-kDa Crk-associated substrate-related protein, and its association of Crk and C3G . The Journal of Biological Chemistry . 273 . 11 . 6446–51 . Mar 1998 . 9497377 . 10.1074/jbc.273.11.6446 . free .
• Astier A, Manié SN, Law SF, Canty T, Haghayghi N, Druker BJ, Salgia R, Golemis EA, Freedman AS . Association of the Cas-like molecule HEF1 with CrkL following integrin and antigen receptor signaling in human B-cells: potential relevance to neoplastic lymphohematopoietic cells . Leukemia & Lymphoma . 28 . 1–2 . 65–72 . Dec 1997 . 9498705 . 10.3109/10428199709058332 .
• Yokote K, Hellman U, Ekman S, Saito Y, Rönnstrand L, Saito Y, Heldin CH, Mori S . Identification of Tyr-762 in the platelet-derived growth factor alpha-receptor as the binding site for Crk proteins . Oncogene . 16 . 10 . 1229–39 . Mar 1998 . 9546424 . 10.1038/sj.onc.1201641 . free .
• Kirsch KH, Georgescu MM, Hanafusa H . Direct binding of p130(Cas) to the guanine nucleotide exchange factor C3G . The Journal of Biological Chemistry . 273 . 40 . 25673–9 . Oct 1998 . 9748234 . 10.1074/jbc.273.40.25673 . free .
• Ichiba T, Hashimoto Y, Nakaya M, Kuraishi Y, Tanaka S, Kurata T, Mochizuki N, Matsuda M . Activation of C3G guanine nucleotide exchange factor for Rap1 by phosphorylation of tyrosine 504 . The Journal of Biological Chemistry . 274 . 20 . 14376–81 . May 1999 . 10318861 . 10.1074/jbc.274.20.14376 . free .
• Nosaka Y, Arai A, Miyasaka N, Miura O . CrkL mediates Ras-dependent activation of the Raf/ERK pathway through the guanine nucleotide exchange factor C3G in hematopoietic cells stimulated with erythropoietin or interleukin-3 . The Journal of Biological Chemistry . 274 . 42 . 30154–62 . Oct 1999 . 10514505 . 10.1074/jbc.274.42.30154 . free .
• Uemura N, Griffin JD . The adapter protein Crkl links Cbl to C3G after integrin ligation and enhances cell migration . The Journal of Biological Chemistry . 274 . 53 . 37525–32 . Dec 1999 . 10608804 . 10.1074/jbc.274.53.37525 . free .

External links

• RAPGEF1 Info with links in the Cell Migration Gateway

Notes and References

1. Takai S, Tanaka M, Sugimura H, Yamada K, Naito Y, Kino I, Matsuda M . Mapping of the human C3G gene coding a guanine nucleotide releasing protein for Ras family to 9q34.3 by fluorescence in situ hybridization . Human Genetics . 94 . 5 . 549–50 . Nov 1994 . 7959692 . 10.1007/bf00211024 . 34197232 .
2. Tanaka S, Morishita T, Hashimoto Y, Hattori S, Nakamura S, Shibuya M, Matuoka K, Takenawa T, Kurata T, Nagashima K . C3G, a guanine nucleotide-releasing protein expressed ubiquitously, binds to the Src homology 3 domains of CRK and GRB2/ASH proteins . Proceedings of the National Academy of Sciences of the United States of America . 91 . 8 . 3443–7 . Apr 1994 . 7512734 . 43593 . 10.1073/pnas.91.8.3443 . 1994PNAS...91.3443T . free .
3. Web site: Entrez Gene: RAPGEF1 Rap guanine nucleotide exchange factor (GEF) 1.
4. Kirsch KH, Georgescu MM, Hanafusa H . Direct binding of p130(Cas) to the guanine nucleotide exchange factor C3G . The Journal of Biological Chemistry . 273 . 40 . 25673–9 . Oct 1998 . 9748234 . 10.1074/jbc.273.40.25673. free .
5. Kyono WT, de Jong R, Park RK, Liu Y, Heisterkamp N, Groffen J, Durden DL . Differential interaction of Crkl with Cbl or C3G, Hef-1, and gamma subunit immunoreceptor tyrosine-based activation motif in signaling of myeloid high affinity Fc receptor for IgG (Fc gamma RI) . Journal of Immunology . 161 . 10 . 5555–63 . Nov 1998 . 10.4049/jimmunol.161.10.5555 . 9820532 . free .
6. Grumbach IM, Mayer IA, Uddin S, Lekmine F, Majchrzak B, Yamauchi H, Fujita S, Druker B, Fish EN, Platanias LC . Engagement of the CrkL adaptor in interferon alpha signalling in BCR-ABL-expressing cells . British Journal of Haematology . 112 . 2 . 327–36 . Feb 2001 . 11167825 . 10.1046/j.1365-2141.2001.02556.x. 85033851 . free .
7. Ahmad S, Alsayed YM, Druker BJ, Platanias LC . The type I interferon receptor mediates tyrosine phosphorylation of the CrkL adaptor protein . The Journal of Biological Chemistry . 272 . 48 . 29991–4 . Nov 1997 . 9374471 . 10.1074/jbc.272.48.29991. free .
8. Chin H, Saito T, Arai A, Yamamoto K, Kamiyama R, Miyasaka N, Miura O . Erythropoietin and IL-3 induce tyrosine phosphorylation of CrkL and its association with Shc, SHP-2, and Cbl in hematopoietic cells . Biochemical and Biophysical Research Communications . 239 . 2 . 412–7 . Oct 1997 . 9344843 . 10.1006/bbrc.1997.7480 .
9. William C. Mobley . Wu C, Lai CF, Mobley WC . Nerve growth factor activates persistent Rap1 signaling in endosomes . The Journal of Neuroscience . 21 . 15 . 5406–16 . Aug 2001 . 11466412 . 10.1523/JNEUROSCI.21-15-05406.2001. 6762651 . free .
10. Sakkab D, Lewitzky M, Posern G, Schaeper U, Sachs M, Birchmeier W, Feller SM . Signaling of hepatocyte growth factor/scatter factor (HGF) to the small GTPase Rap1 via the large docking protein Gab1 and the adapter protein CRKL . The Journal of Biological Chemistry . 275 . 15 . 10772–8 . Apr 2000 . 10753869 . 10.1074/jbc.275.15.10772. free .
11. Smit L, van der Horst G, Borst J . Sos, Vav, and C3G participate in B cell receptor-induced signaling pathways and differentially associate with Shc-Grb2, Crk, and Crk-L adaptors . The Journal of Biological Chemistry . 271 . 15 . 8564–9 . Apr 1996 . 8621483 . 10.1074/jbc.271.15.8564. free .
12. Shivakrupa R, Radha V, ((Sudhakar Ch)), Swarup G . Physical and functional interaction between Hck tyrosine kinase and guanine nucleotide exchange factor C3G results in apoptosis, which is independent of C3G catalytic domain . The Journal of Biological Chemistry . 278 . 52 . 52188–94 . Dec 2003 . 14551197 . 10.1074/jbc.M310656200 . free .