Signalling to actin: Role of C3G, a multitasking guanine-nucleotide- exchange factor

Bioscience Reports

Volumn 31, Issue 4, 2011, Pages 231-244

  Radha, Vegesna ^a   Mitra, Aninda ^a   Dayma, Kunal ^a   Sasikumar, Kotagiri ^a  

^a CENTRE FOR CELLULAR AND MOLECULAR BIOLOGY   (India)

Author keywords

Actin cytoskeleton; C3G (Crk SH3 domain binding guanine nucleotide releasing factor); Differentiation; Embryonic development; GTPase; Signalling

Indexed keywords

ACTIN; CRK SH3 DOMAIN BINDING GUANINE NUCLEOTIDE EXCHANGE FACTOR; GUANINE NUCLEOTIDE EXCHANGE FACTOR; GUANOSINE TRIPHOSPHATASE; RAP1 PROTEIN; RAP2 PROTEIN; RAS PROTEIN; RHO GUANINE NUCLEOTIDE BINDING PROTEIN; TC21 PROTEIN; UNCLASSIFIED DRUG; MONOMERIC GUANINE NUCLEOTIDE BINDING PROTEIN;

AGYRIA; APOPTOSIS; CELL ADHESION; CELL DIFFERENTIATION; CELL FUNCTION; CELL JUNCTION; CELL MIGRATION; CELL PROLIFERATION; CELL SURVIVAL; CELL TRANSFORMATION; CELL TRANSPORT; CELL TYPE; CELL VACUOLE; CHRONIC MYELOID LEUKEMIA; CYTOSKELETON; DISEASE ASSOCIATION; EMBRYO DEVELOPMENT; ENZYME ACTIVATION; FILOPODIUM; GLOMERULONEPHRITIS; HUMAN; LUNG NON SMALL CELL CANCER; MALIGNANT TRANSFORMATION; MAMMAL; NERVE FIBER GROWTH; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PATHOGENESIS; PROTEIN EXPRESSION; PROTEIN FAMILY; PROTEIN FUNCTION; PROTEIN INTERACTION; REVIEW; SIGNAL TRANSDUCTION; SINGLE NUCLEOTIDE POLYMORPHISM; UTERINE CERVIX CARCINOMA; ANIMAL; BIOLOGICAL MODEL; CHEMISTRY; GENETICS; METABOLISM;

MAMMALIA;

ACTINS; ANIMALS; APOPTOSIS; CELL PROLIFERATION; CELL SURVIVAL; CYTOSKELETON; GUANINE NUCLEOTIDE-RELEASING FACTOR 2; HUMANS; MODELS, BIOLOGICAL; MONOMERIC GTP-BINDING PROTEINS; SIGNAL TRANSDUCTION;

EID: 79960113049     PISSN: 01448463     EISSN: None     Source Type: Journal    
DOI: 10.1042/BSR20100094     Document Type: Review

References (108)

1. Bos, J. L., Rehmann, H. and Wittinghofer, A. (2007) GEFs and GAPs: critical elements in the control of small G proteins. Cell 129, 865-877 (Pubitemid 46802708)
2. Raaijmakers, J. H. and Bos, J. L. (2009) Specificity in Ras and Rap signaling. J. Biol. Chem. 284, 10995-10999
3. Quilliam, L. A., Rebhun, J. F. and Castro, A. F. (2002) A growing family of guanine nucleotide exchange factors is responsible for activation of Ras-family GTPases. Prog. Nucleic Acid Res. Mol. Biol. 71, 391-444
4. Tanaka, S., Morishita, T., Hashimoto, Y., Hattori, S., Nakamura, S., Shibuya, M., Matuoka, K., Takenawa, T., Kurata, T., Nagashima, K. et al. (1994) C3G, a guanine nucleotide-releasing protein expressed ubiquitously, binds to the Src homology 3 domains of CRK and GRB2/ASH proteins. Proc. Natl. Acad. Sci. U.S.A. 91, 3443-3447
5. Knudsen, B. S., Feller, S. M. and Hanafusa, H. (1994) Four proline-rich sequences of the guanine-nucleotide exchange factor C3G bind with unique specificity to the first Src homology 3 domain of Crk. J. Biol. Chem. 269, 32781-32787
6. Kirsch, K. H., Georgescu, M. M. and Hanafusa, H. (1998) Direct binding of p130(Cas) to the guanine nucleotide exchange factor C3G. J. Biol. Chem. 273, 25673-25679
7. Shivakrupa, R., Radha, V., Sudhakar, C. and Swarup, G. (2003) Physical and functional interaction between Hck tyrosine kinase and guanine nucleotide exchange factor C3G results in apoptosis, which is independent of C3G catalytic domain. J. Biol. Chem. 278, 52188-52194
8. Radha, V., Rajanna, A., Mitra, A., Rangaraj, N. and Swarup, G. (2007) C3G is required for c-Abl-induced filopodia and its overexpression promotes filopodia formation. Exp. Cell Res. 313, 2476-2492
9. Hogan, C., Serpente, N., Cogram, P., Hosking, C. R., Bialucha, C. U., Feller, S. M., Braga, V. M., Birchmeier, W. and Fujita, Y. (2004) Rap1 regulates the formation of E-cadherin-based cell-cell contacts. Mol. Cell. Biol. 24, 6690-6700
10. Takai, S, Tanaka, M, Sugimura, H, Yamada, K, Naito, Y, Kino, I and Matsuda, M. (1994) Mapping of the human C3G gene coding a guanine nucleotide releasing protein for Ras family to 9q34.3 by fluorescence in situ hybridization. Hum. Genet. 94, 549-550 (Pubitemid 24340671)
11. Gotoh, T., Hattori, S., Nakamura, S., Kitayama, H., Noda, M., Takai, Y., Kaibuchi, K., Matsui, H., Hatase, O., Takahashi, H. et al. (1995) Identification of Rap1 as a target for the Crk SH3 domain-binding guanine nucleotide-releasing factor C3G. Mol. Cell. Biol. 15, 6746-6753
12. Gotoh, T., Niino, Y., Tokuda, M., Hatase, O., Nakamura, S., Matsuda, M. and Hattori, S. (1997) Activation of R-Ras by Ras-guanine nucleotide-releasing factor. J. Biol. Chem. 272, 18602-18607
13. van den Berghe, N., Cool, R. H., Horn, G. and Wittinghofer, A. (1997) Biochemical characterization of C3G: an exchange factor that discriminates between Rap1 and Rap2 and is not inhibited by Rap1A(S17N). Oncogene 15, 845-850 (Pubitemid 27390137)
14. York, R. D., Yao, H., Dillon, T., Eilig, C. L., Eckert, S. P., McCleskey, E. W. and Stork, P. J. (1998) Rap1 mediates sustained MAPK activation induced by NGF. Nature 392, 622-626 (Pubitemid 28207722)
15. Mochizuki, N., Ohba, Y., Kobayashi, S., Otsuka, N., Graybiel, A. M., Tanaka, S. and Matsuda, M. (2000) Crk activation of JNK via C3G and R-Ras. J. Biol. Chem. 275, 12667-12671
16. Ohba, Y., Mochizuki, N., Yamashita, S., Chan, A. M., Schrader, J. W., Hattori, S., Nagashima, K. and Matsuda, M. (2000) Regulatory proteins of R-Ras, TC21/R-Ras2, and M-Ras/R-Ras3. J. Biol. Chem. 275, 20020-20026
17. Chiang, S. H., Baumann, C. A., Kanzaki, M., Thurmond, D. C., Watson, R. T., Neudauer, C. L., Macara, I. G., Pessin, J. E. and Saltiel, A. R. (2001) Insulin-stimulated GLUT4 translocation requires the CAP-dependent activation of TC10. Nature 410, 944-948
18. Ling, L., Zhu, T. and Lobie, P. E. (2003) Src-Crkll-C3G-dependent activation of Rap1 switches growth hormone-stimulated p44/42 MAP kinase and JNK/SAPK activities. J. Biol. Chem. 278, 27301-27311
19. Wang, Z., Dillon, T. J., Pokala, V., Mishra, S., Labudda, K., Hunter, B. and Stork, P. J. (2006) Rap1-mediated activation of extracellular signal-regulated kinases by cyclic AMP is dependent on the mode of Rap1 activation. Mol. Cell. Biol. 26, 2130-2145
20. Shivakrupa, R., Singh, R. and Swarup, G. (1999) Identification of a novel splice variant of C3G which shows tissue-specific expressionDNA Cell Biol. 18, 701-708
21. Gutierrez-Berzal, J., Castellano, E., Martin-Encabo, S., Gutierrez-Cianca, N., Hernandez, J. M., Santos, E. and Guerrero, C. (2006) Characterization of p87C3G, a novel, truncated C3G isoform that is overexpressed in chronic myeloid leukemia and interacts with Bcr-Abl. Exp. Cell Res. 312, 938-948
22. Zhai, B., Huo, H. and Liao, K. (2001) C3G, a guanine nucleotide exchange factor bound to adapter molecule c-Crk, has two alternative splicing forms. Biochem. Biophys. Res. Commun. 286, 61-66
23. Radha, V., Rajanna, A., Gupta, R. K., Dayma, K. and Raman, T. (2008) The guanine nucleotide exchange factor, C3G regulates differentiation and survival of human neuroblastoma cells. J. Neurochem. 107, 1424-1435
24. Prince, L. S., Karp, P. H., Moninger, T. O. and Welsh, M. J. (2001) KGF alters gene expression in human airway epithelia: potential regulation of the inflammatory response. Physiol. Genom. 6, 81-89
25. Okino, K., Nagai, H., Nakayama, H., Doi, D., Yoneyama, K., Konishi, H. and Takeshita, T. (2006) Inactivation of Crk SH3 domain-binding guanine nucleotide-releasing factor (C3G) in cervical squamous cell carcinoma. Int. J. Gynecol. Cancer 16, 763-771
26. Wang, H., Linghu, H., Wang, J., Che, Y. L., Xiang, T. X., Tang, X. and Yao, Z. W. (2010) The role of Crk/Dock180/Rac1 pathway in the malignant behavior of human ovarian cancer cell SKOV3. Tumour Biol. 31, 59-67
27. Ichiba, T., Hashimoto, Y., Nakaya, M., Kuraishi, Y., Tanaka, S., Kurata, T., Mochizuki, N. and Matsuda, M. (1999) Activation of C3G guanine nucleotide exchange factor for Rap1 by phosphorylation of tyrosine 504. J. Biol. Chem. 274, 14376-14381
28. Radha, V., Rajanna, A. and Swarup, G. (2004) Phosphorylated guanine nucleotide exchange factor C3G, induced by pervanadate and Src family kinases localizes to the Golgi and subcortical actin cytoskeleton. BMC Cell Biol. 5, 31
29. Nolz, J. C., Nacusi, L. P., Segovis, C. M., Medeiros, R. B., Mitchell, J. S., Shimizu, Y. and Billadeau, D. D. (2008) The WAVE2 complex regulates T cell receptor signaling to integrins via Abl- and CrkL-C3G-mediated activation of Rap1. J. Cell Biol. 182, 1231-1244
30. Mitra, A. and Radha, V. (2010) F-actin-binding domain of c-Abl regulates localized phosphorylation of C3G: role of C3G in c-Abl-mediated cell death. Oncogene 29, 4528-4542
31. Yokote, K., Hellman, U., Ekman, S., Saito, Y., Ronnstrand, L., Heldin, C. H. and Mori, S. (1998) Identification of Tyr-762 in the platelet-derived growth factor alpha-receptor as the binding site for Crk proteins. Oncogene 16, 1229-1239 (Pubitemid 28138195)
32. Larsson, H., Klint, P., Landgren, E. and Claesson-Welsh, L. (1999) Fibroblast growth factor receptor-mediated endothelial cell proliferation is dependent on the Src homology (SH) 2/SH3 domain containing adaptor protein. J. Biol. Chem. 274, 25726-25734
33. Uemura, N. and Griffin, J. D. (1999) The adapter protein Crkl links Cbl to C3G after integrin ligation and enhances cell migration. J. Biol. Chem. 274, 37525-37532
34. Sakkab, D., Lewitzky, M., Posern, G., Schaeper, U., Sachs, M., Birchmeier, W. and Feller, S. M. (2000) Signaling of hepatocyte growth factor/scatter factor (HGF) to the small GTPase Rap1 via the large docking protein Gab1 and the adapter protein CRKL. J. Biol. Chem. 275, 10772-10778
35. Ichiba, T., Kuraishi, Y., Sakai, O., Nagata, S., Groffen, J., Kurata, T., Hattori, S. and Matsuda, M. (1997) Enhancement of guanine-nucleotide exchange activity of C3G for Rap1 by the expression of Crk, CrkL, and Grb2. J. Biol. Chem. 272, 22215-22220 (Pubitemid 27382852)
36. Okada, S., Matsuda, M., Anafi, M., Pawson, T. and Pessin, J. E. (1998) Insulin regulates dynamic balance between Ras and Rap1 signaling by coordinating assembly states of Grb2-SOS and Crkll-C3G complexes. EMBO J. 17, 2554-2565
37. Takino, T., Tamura, M., Miyamori, H., Araki, M., Matsumoto, K., Sato, H. and Yamada, K. M. (2003) Tyrosine phosphorylation of the Crkll adaptor protein modulates cell migration. J. Cell Sci. 116, 3145-3155
38. Tanaka, S., Ouchi, T. and Hanafusa, H. (1997) Downstream of Crk adaptor signaling pathway: activation of Jun kinase by v-Crk through the guanine nucleotide exchange protein C3G. Proc. Natl. Acad. Sci. U.S.A. 94, 2356-2361
39. Buensuceso, C. S. and O'Toole, T. E. (2000) The association of CRKII with C3G can be regulated by integrins and defines a novel means to regulate the mitogen-activated protein kinases. J. Biol. Chem. 275, 13118-13125
40. Zhang, W., Shao, Y., Fang, D., Huang, J., Jeon, M. S. and Liu, Y. C. (2003) Negative regulation of T-cell antigen receptor mediated Crk-L-C3G signalling and cell adhesion by cbl-b. J. Biol. Chem. 278, 23978-23983
41. Fecchi, K., Volonte, D., Hezel, M. P., Schmeck, K. and Galbiati, F. (2006) Spatial and temporal regulation of GLUT4 translocation by flotillin-1 and caveolin-3 in skeletal muscle cells. FASEB J. 20, 705-707 (Pubitemid 46671188)
42. Deevi, R. K., Koney-Dash, M., Kissenpfennig, A., Johnston, J. A., Schuh, K., Walter, U. and Dib, K. Vasodilator-stimulated phosphoprotein regulates inside-out signaling of β2 integrins in neutrophils. J. Immunol. 184, 6575-6584
43. de Jong, R., van Wijk, A., Heisterkamp, N. and Groffen, J. (1998) C3G is tyrosine-phosphorylated after integrin-mediated cell adhesion in normal but not in Bcr/Abl expressing cells. Oncogene 17, 2805-2810 (Pubitemid 28554240)
44. Cho, Y. J., Hemmeryckx, B., Groffen, J. and Heisterkamp, N. (2005) Interaction of Bcr/Abl with C3G, an exchange factor for the small GTPase Rap1, through the adapter protein Crkl. Biochem. Biophys. Res. Commun. 333, 1276-1283
45. Martin-Encabo, S., Santos, E. and Guerrero, C. (2007) C3G mediated suppression of malignant transformation involves activation of PP2A phosphatases at the subcortical actin cytoskeleton. Exp. Cell Res. 313, 3881-3891
46. Bivona, T. G., Wiener, H. H., Ahearn, I. M., Silletti, J., Chiu, V. K. and Philips, M. R. (2004) Rap1 up-regulation and activation on plasma membrane regulates T cell adhesion. J. Cell Biol. 164, 461-470
47. Okada, S. and Pessin, J. E. (1997) Insulin and epidermal growth factor stimulate a conformational change in Rap1 and dissociation of the Crkll-C3G complex. J. Biol. Chem. 272, 28179-28182
48. Kao, S., Jaiswal, R. K., Kolch, W. and Landreth, G. E. (2001) Identification of the mechanisms regulating differential activation of the MAPK cascade by EGF and NGF in PC12 cells. J. Biol. Chem. 276, 18169-18177
49. Li, L., Okura, M. and Imamoto, A. (2002) Focal adhesions require catalytic activity of Src family kinases to mediate integrin-matrix adhesion. Mol. Cell. Biol. 22, 1203-1217
50. Kyono, W. T., de Jong, R., Park, R. K., Liy, Y., Heisterkamp, N., Groffen, J. and Durden, D. L. (1998) Differential interaction of Crk1 with Cbl or C3G, Hef-1, and γ subunit immunoreceptor tyrosine-based activation motif in signaling of myeloid high affinity Fc receptor for IgG (FcγRI). J. Immunol. 161, 5555-5563
51. Uemura, N., Salgia, R., Li, J. L., Pisick, E., Sattler, M. and Griffin, J. D. (1997) The BCR/ABL oncogene alters interaction of the adapter proteins CRKL and CRK with cellular proteins. Leukemia 11, 376-385
52. Takahashi, M., Rikitake, Y., Nagamatsu, Y., Hara, T., Ikeda, W., Hirata, K. and Takai, Y. (2008) Sequential activation of Rap1 and Rac1 small G proteins by PDGF locally at leading edges of NIH3T3 cells. Genes Cells 13, 549-569 (Pubitemid 351761773)
53. Ohba, Y., Ikuta, K., Ogura, A., Matsuda, J., Mochizuki, N., Nagashima, K., Kurokawa, K., Mayer, B. J., Maki, K., Miyazaki, J. et al. (2001) Requirement for C3G-dependent Rap1 activation for cell adhesion and embryogenesis. EMBO J. 20, 3333-3341 (Pubitemid 32634341)
54. Voss, A. K., Gruss, P. and Thomas, T. (2003) The guanine nucleotide exchange factor C3G is necessary for the formation of focal adhesions and vascular maturation. Development 130, 355-367 (Pubitemid 36175933)
55. Voss, A. K., Krebs, D. L. and Thomas, T. (2006) C3G regulates the size of the cerebral cortex neural precursor population. EMBO J. 25, 3652-3663 (Pubitemid 44264875)
56. Voss, A. K., Britto, J. M., Dixon, M. P., Sheikh, B. N., Collin, C., Tan, S. S. and Thomas, T. (2008) C3G regulates cortical neuron migration, preplate splitting and radial glial cell attachment. Development 135, 2139-2149 (Pubitemid 352015148)
57. Ishimaru, S., Williams, R., Clark, E., Hanafusa, H. and Gaul, U. (1999) Activation of the Drosophila C3G leads to cell fate changes and overproliferation during development, mediated by the RAS-MAPK pathway and RAP1. EMBO J. 18, 145-155
58. Shirinian, M., Grabbe, C., Popovic, M., Varshney, G., Hugosson, F., Bos, H., Rehmann, H. and Palmer, R. H. (2010) The Rap1 guanine nucleotide exchange factor C3G is required for preservation of larval muscle integrity in Drosophila melanogaster. PLoS One 5, e9403
59. Luber, B., Candidus, S., Handschuh, G., Mentele, Edith, Hutzler, P., Feller, S., Voss, J., Hofler, H. and Becke, K. F. (2000) Tumor-derived mutated E-cadherin influences β-catenin localization and increases susceptibility to actin cytoskeletal changes induced by pervanadate. Cell Commun. Adhesion 7, 391-408
60. Tamada, M., Sheetz, M. P. and Sawada, Y. (2004) Activation of a signaling cascade by cytoskeleton stretch. Dev. Cell 7, 709-718 (Pubitemid 39462691)
61. Lee, H., Gaughan, J. P. and Tsygankov, A. Y. (2008) c-Cbl facilitates cytoskeletal effects in v-Abl transformed fibroblast through Rac1 and Rap1-mediated signaling. Int. Biochem. Cell Biol. 40, 1930-1943
62. Kanzaki, M., Watson, R. T., Hou, J. C., Stamnes, M., Saltiel, A. R. and Pessin, J. E. (2002) Small GTP-binding protein TC10 differentially regulates two distinct populations of filamentous actin in 3T3L1 adipocytes. Mol. Biol. Cell 13, 2334-2346
63. Balzac, F., Avolio, M., Degani, S., Kaverina, I., Torti, M., Silengo, L., Small, J. V. and Retta, S. F. (2005) E-cadherin endocytosis regulates the activity of Rap1: a traffic light GTPase at the crossroads between Cadherin and integrin function. J. Cell Sci. 118, 4765-4783
64. Laviolette, M. J., Nunes, P., Peyre, J. B., Aigaki, T. and Stewart, B. A. (2005) A genetic screen for suppressors of Drosophila NSF2 neuromuscular junction overgrowth. Genetics 170, 779-792
65. McLeod, S. J., Shum, A. J., Lee, R. L., Takei, F. and Gold, M. R. (2004) The Rap GTPases regulate integrin-mediated adhesion, cell spreading, actin polymerization, and Pyk2 tyrosine phosphorylation in B lymphocytes. J. Biol. Chem. 279, 12009-12019
66. Fukuyama, T., Ogita, H., Kawakatsu, T., Fukuhara, T., Yamada, T., Sato, T., Shimizu, K., Nakamura, T., Matsuda, M. and Takai, Y. (2001) Involvement of c-Src-Crk-C3G-C3G-Rap1 signaling in the nectin induced activation of Cdc42 and formation of adherens junctions. J. Biol. Chem. 280, 815-825
67. Abe, T., Kato, M., Miki, H., Takenawa, T. and Endo, T. (2003) Small GTPase Tc10 and its homologue RhoT induce N-WASP-mediated long process formation and neurite outgrowth. J. Cell Sci. 116, 155-168 (Pubitemid 36113974)
68. Ridley, A. J. (2006) Rho GTPases and actin dynamics in membrane protrusions and vesicle trafficking. Trends Cell Biol. 16, 522-529
69. Pommereit, D. and Wouters, F. S. (2007) An NGF-induced Exo70-TC10 complex locally antagonises Cdc42-mediated activation of N-WASP to modulate neurite outgrowth. J. Cell Sci. 120, 2694-2705 (Pubitemid 47323876)
70. Gawecka, J. E., Griffiths, G. S., Ek-Rylander, B., Ramos, J. W. and Matter, M. L. (2010) R-Ras regulates migration through an interaction with filamin A in melanoma cells. PLoS One 5, e11269
71. Ada-Nguema, A. S., Xenias, H., Hofman, J. M., Wiggins, C. H., Sheetz, M. P. and Keely, P. J. (2006) The small GTPase R-Ras regulates organization of actin and drives membrane protrusions through the activity of PLCε. J. Cell Sci. 119, 1307-1319
72. Jeong, H. W., Nam, J. O. and Kim, I. S. (2005) The C-terminal end of R-Ras alters the motility and morphology of breast epithelial cells through Rho/Rho kinase. Can. Res. 65, 507-515
73. Holly, S. P., Barson, M. K. and Parise, L. V. (2005) The unique N-terminus of R-Ras is required for Rac activation and precise regulation of cell migration. Mol. Biol. Cell 16, 2458-2469
74. Xu, J., Shi, S., Matsumoto, N., Noda, M. and Kitayama, H. (2007) Identification of Rgl3 as a potential binding partner for Rap-family small G-proteins and profilin II. Cell Signalling 19, 1575-1582 (Pubitemid 46818920)
75. Taira, K., Umikawa, M., Takei, K., Myagmar, B. E., Shinzato, M., Machida, N., Uezato, H., Nonaka, S. and Kariya, K. (2004) The Traf2- and Nck-interacting kinase as a putative effector of Rap2 to regulate actin cytoskeleton. J. Biol. Chem. 279, 49488-49496
76. Pannekoek, W. J., Kooistra, M. R., Zwartkruis, F. J. and Bos, J. L. (2009) Cell-cell junction formation: the role of Rap1 and Rap1 guanine nucleotide exchange factors. Biochim. Biophys. Acta 1788, 790-796
77. Tsukamoto, N., Hattori, M., Yang, H., Bos, J. L. and Minato, N. (1999) Rap1 GTPase-activating protein SPA-1 negatively regulates cell adhesion. J. Biol. Chem. 274, 18463-18469
78. Arai, A., Nosaka, Y., Kohsaka, H., Miyasaka, N. and Miura, O. (1999) CrkL activates integrin-mediated hematopoietic cell adhesion through the guanine nucleotide exchange factor C3G. Blood 93, 3713-3722 (Pubitemid 29249818)
79. Guerrero, C., Martin-Encabo, S., Fernandez-Medarde, A. and Santos, E. (2004) C3G-mediated suppression of oncogene-induced focus formation in fibroblasts involves inhibition of ERK activation, cyclin A expression and alterations of anchorage-independent growth. Oncogene 23, 4885-4893 (Pubitemid 38932160)
80. Nievers, M. G., Birge, R. B., Greulich, H., Verkleij, A. J., Hanafusa, H. and van Bergen en Henegouwen, P. M. (1997) v-Crk-induced cell transformation: changes in focal adhesion composition and signaling. J Cell Sci. 110, 389-399
81. Oh, J., Seo, D. W., Diaz, T., Wei, B., Ward, Y., Ray, J. M., Morioka, Y., Shi, S., Kitayama, H., Takahashi, C., Noda, M. and Stetler-Stevenson, W. G. (2004) Tissue inhibitors of metalloproteinase 2 inhibits endothelial cell migration through increased expression of RECK. Cancer Res. 64, 9062-9069
82. Wang, S. F., Aoki, M., Nakashima, Y., Shinozuka, Y., Tanaka, H., Taniwaki, M., Hattori, M. and Minato, N. (2008) Development of Notch-dependent T-cell leukemia by deregulated Rap1 signaling. Blood 111, 2878-2886
83. Schonherr, C., Yang, H. L., Vigny, M., Palmer, R. H. and Hallberg, B. (2010) Anaplastic lymphoma kinase activates the smalt GTPase Rap1 via the Rap1-specific GEF C3G in both neuroblastoma and PC12 cells. Oncogene 29, 2817-2830
84. Jin, S., Zhai, B., Qiu, Z., Wu, J., Lane, M. D. and Liao, K. (2000) c-Crk, a substrate of the insulin-like growth factor-1 receptor tyrosine kinase, functions as an early signal mediator in adipocyte differentiation process. J. Biol. Chem. 275, 34444-34452
85. De Falco, V., Castellone, M. D., De Vita, G., Cirafici, A. M., Hershman, J. M., Guerrero, C., Fusco, A., Melillo, R. M. and Santoro, M. (2007) RET/papillary thyroid carcinoma oncogenic signaling through the Rap1 small GTPase. Cancer Res. 67, 381-390 (Pubitemid 46142797)
86. Guerrero, C., Fernandez-Medarde, A., Rojas, J. M., Font de Mora, J., Esteban, L. M. and Santos, E. (1998) Transformation suppressor activity of C3G is independent of its CDC25-homology domain. Oncogene 16, 613-624 (Pubitemid 28062341)
87. Gutierrez-Uzquiza, A., Arechederra, M., Molina, I., Banos, R., Maia, V., Benito, M., Guerrero, C. and Porras, A. (2010) C3G down-regulates p38 MAPK activity in response to stress by Rap-1 independent mechanisms: involvement in cell death. Cell Signalling 22, 533-542
88. Maia, V., Sanz, M., Gutierrez-Berzal, J., de Luis, A., Gutierrez-Uzquiza, A., Porras, A. and Guerrero, C. (2009) C3G silencing enhances STI-571-induced apoptosis in CML cells through p38 MAPK activation, but it antagonizes STI-571 inhibitory effect on survival. Cell Signalling 21, 1229-1235
89. Asuri, S., Yan, J., Paranavitana, N. C. and Quilham, L. A. (2008) E-cadherin disengagement activates Rap1 GTPase. J. Cell Biochem. 105, 1027-1037
90. Sato, T., Fujita, N., Yamada, A., Ooshio, T., Okamoto, R., Irie, K. and Takai, Y. (2006) Regulation of the assembly and adhesion activity of E-cadherin by nectin and afadin for the formation of adherens junctions in Madin-Darby canine kidney cells. J. Biol. Chem. 281, 5288-5299
91. Hirata, T., Nagai, H., Koizumi, K., Okino, K., Harada, A., Onda, M., Nagahata, T., Mikami, I., Hirai, K., Haraguchi, S. et al. (2004) Amplification, up-regulation and over-expression of C3G (CRK SH3 domain-binding guanine nucleotide-releasing factor) in non-small cell lung cancers. J. Hum. Genet. 49, 290-295
92. Fernandez, V., Jares, P., Salaverria, I., Gine, E., Bea, S., Aymerich, M., Colomer, D., Villamor, N., Bosch, F., Montserrat, E. et al. (2008) Gene expression profile and genomic changes in disease progression of early-stage chronic lymphocytic leukemia. Haematologica 93, 132-136 (Pubitemid 351156163)
93. Virgili, A., Brazma, D., Reid, A. G., Howard-Reeves, J., Valgañóon, M., Chanalaris, A., De Melo, V. A., Marin, D., Apperley, J. F. and Grace, C. (2008) FISH mapping of Philadelphia negative BCR/ABL1 positive CML. Mol. Cytogenet. 1, 14
94. Gaulton, K. J., Willer, C. J., Li, Y., Scott, L. J., Conneely, K. N., Jackson, A. U., Duren, W. L., Chines, P. S., Narisu, N., Bonnycastle, L. L. et al. (2008) Comprehensive association study of type 2 diabetes and related quantitative traits with 222 candidate genes. Diabetes 57, 3136-3144
95. Hong, K. W., Jin, H. S., Lim, J. E., Ryu, H. J., Go, M. J., Lee, J. Y., Woo, J. T., Park, H. K. and Oh, B. (2009) RAPGEF1 gene variants associated with type 2 diabetes in the Korean population. Diabetes Res. Clin. Pract. 84, 117-122
96. Rufanova, V. A., Lianos, E., Alexanian, A., Sorokina, E., Sharma, M., McGinty, A. and Sorokin, A. (2009) C3G overexpression in glomerular epithelial cells during anti-GBM-induced glomerulonephritis. Kidney Int. 75, 31-40
97. Nowak, N. J., Sait, S. N., Zeidan, A., Deeb, G., Gaile, D., Liu, S., Ford, L., Wallace, P. K., Wang, E. S. and Wetzler, M. (2010) Recurrent deletion of 9q34 in adult normal karyotype precursor B-cell ALL. Can. Genet. Cytogenet. 199, 15-20
98. Arai, A., Nosaka, Y., Kanda, E., Yamamoto, K., Miyasaka, N. and Miura, O. (2001) Rap1 is activated by erythropoietin or interleukin-3 and is involved in regulation of βl integrin-mediated hematopoietic cell adhesion. J. Biol. Chem. 276, 10453-10462
99. Reedquist, K. A., Fukazawa, T., Panchamoorthy, G., Langdon, W. Y., Shoelson, S. E., Druker, B. J. and Band, H. (1996) Stimulation through the T-cell receptor induces CbI association with Crk proteins and the guanine nucleotide exchange protein C3G. J. Biol. Chem. 271, 8435-8442
100. Smit, L., van der Horst, G. and Borst, J. (1996) Sos, Vav, and C3G participate in B-cell receptor-inducing signaling pathways and differentially associate with Shc-Grb2, Crk, and Crk-L adaptors. J. Biol. Chem. 271, 8564-8569
101. Alsayed, Y., Uddin, S., Ahmad, S., Majchrzak, B., Druker, B. J., Fish, E. N. and Platimas, L. C. (2000) IFN-γ activates C3G/Rap1 signaling pathway. J. Immunol. 164, 1800-1806
102. Nasaka, Y., Arai, A., Miyasaka, N. and Miura, O. (1999) CrkL mediates Ras-dependent activation of the Raf/ERK pathway through the GEF, C3G in hematopoietic cells stimulated with EPO and IL-3. J. Biol. Chem. 274, 30154-30162
103. Du, J., AlSayed, Y. M., Xin, F., Ackerman, S. J. and Platanias, L. C. (2000) Engagement of the CrkL adapter in IL-5 signaling in eosinophils. J. Biol. Chem. 275, 33167-33175
104. Ballif, B. A., Arnaud, L., Arthur, W. T., Guris, D., Imamoto, A. and Cooper, J. A. (2004) Activation of a Dab1/CrkL/C3G/Rap1 pathway in Reelin-stimulated neurons. Curr. Biol. 14, 606-610
105. Fukuyama, T., Ogita, H., Kawakatsu, T., Inagaki, M. and Takai, Y. (2006) Activation of Rac by cadherin through the c-Src-Rap1-phosphatidylinositol 3-kinase-Vav2 pathway. Oncogene 25, 8-19 (Pubitemid 43049999)
106. Posern, G., Rapp, U. R. and Feller, S. M. (2000) The Crk signaling pathway contributes to the bombesin-induced activation of the small GTPase Rap1 in Swiss 3T3 cells. Oncogene 19, 6361-6368
107. Boriack-Sjodin, P. A., Margarit, S. M., Bar-Sagi, D. and Kuriyan, J. (1998) The structural basis of the activation of Ras by Sos. Nature 394, 337-43 (Pubitemid 28373822)
108. van den Berghe, N., Cool, R. H. and Wittinghofer, A. (1999) Discriminatory residues in Ras and Rap for guanine nucleotide exchange factor recognition. J. Biol. Chem. 274, 11078-11085