Cell Growth & Differentiation, Vol 7, Issue 11 1443-1451, Copyright © 1996 by American Association of Cancer Research

ARTICLES

A role for Ras in v-Crk transformation

H Greulich and H Hanafusa
Laboratory of Molecular Oncology, Rockefeller University, New York, New York 10021, USA.

The v-crk oncogene, identified as the transforming gene of the CT10 avian sarcoma virus, encodes an adaptor protein capable of transforming chicken embryo fibroblasts (CEFs). Because the Src homology 3 domain of v-Crk is capable of binding the Ras family guanine nucleotide exchange factors Sos and C3G, the contribution of cellular Ras to signaling by v-Crk was evaluated. NIH-3T3 cell lines stably expressing the v-crk oncogene exhibited a transformed phenotype similar to that of CT10-infected CEFs. Treatment of these cells with a farnesylation inhibitor, as well as coexpression of dominant negative Ras, caused morphological reversion of the v-Crk NIH-3T3 cells. Dominant negative Ras expression also inhibited colony formation in soft agar without affecting tyrosine phosphorylation of cellular proteins. Although elevation of basal Erk activity could be demonstrated in v-Crk-transformed CEFs, no significant elevation of basal Erk activity was observed in the v-Crk-transformed NIH-3T3 cells. This suggests that v-Crk requires Ras function for transformation of NIH-3T3 cells and may utilize a Ras effector other than Erk to maintain the transformed phenotype.

This article has been cited by other articles:

				T. Akagi, K. Murata, T. Shishido, and H. Hanafusa v-Crk Activates the Phosphoinositide 3-Kinase/AKT Pathway by Utilizing Focal Adhesion Kinase and H-Ras Mol. Cell. Biol., October 15, 2002; 22(20): 7015 - 7023. [Abstract] [Full Text] [PDF]

				M. Tsuda, S. Tanaka, H. Sawa, H. Hanafusa, and K. Nagashima Signaling Adaptor Protein v-Crk Activates Rho and Regulates Cell Motility in 3Y1 Rat Fibroblast Cell Line Cell Growth Differ., March 1, 2002; 13(3): 131 - 139. [Abstract] [Full Text] [PDF]

				B. Hemmeryckx, A. van Wijk, A. Reichert, V. Kaartinen, Ron de Jong, P. K. Pattengale, I. Gonzalez-Gomez, J. Groffen, and N. Heisterkamp Crkl Enhances Leukemogenesis in BCR/ABL P190 Transgenic Mice Cancer Res., February 1, 2001; 61(4): 1398 - 1405. [Abstract] [Full Text]

				E. Liu, A. A. Thant, F. Kikkawa, H. Kurata, S. Tanaka, A. Nawa, S. Mizutani, S. Matsuda, H. Hanafusa, and M. Hamaguchi The Ras-Mitogen-activated Protein Kinase Pathway Is Critical for the Activation of Matrix Metalloproteinase Secretion and the Invasiveness in v-crk-transformed 3Y1 Cancer Res., May 1, 2000; 60(9): 2361 - 2364. [Abstract] [Full Text]

				C.-S. Shi, J. Tuscano, and J. H. Kehrl Adaptor proteins CRK and CRKL associate with the serine/threonine protein kinase GCKR promoting GCKR and SAPK activation Blood, February 1, 2000; 95(3): 776 - 782. [Abstract] [Full Text] [PDF]

				Y. Nosaka, A. Arai, N. Miyasaka, and O. Miura 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 J. Biol. Chem., October 15, 1999; 274(42): 30154 - 30162. [Abstract] [Full Text] [PDF]

				E. A. Feshchenko, W. Y. Langdon, and A. Y. Tsygankov Fyn, Yes, and Syk Phosphorylation Sites in c-Cbl Map to the Same Tyrosine Residues That Become Phosphorylated in Activated T Cells J. Biol. Chem., April 3, 1998; 273(14): 8323 - 8331. [Abstract] [Full Text] [PDF]

				R. L. Klemke, J. Leng, R. Molander, P. C. Brooks, K. Vuori, and D. A. Cheresh CAS/Crk Coupling Serves as a "Molecular Switch" for Induction of Cell Migration J. Cell Biol., February 23, 1998; 140(4): 961 - 972. [Abstract] [Full Text] [PDF]

				V. A. Blakesley, D. Beitner-Johnson, J. R. Van Brocklyn, S. Rani, Z. Shen-Orr, B. S. Stannard, S. Spiegel, and D. LeRoith Sphingosine 1-Phosphate Stimulates Tyrosine Phosphorylation of Crk J. Biol. Chem., June 27, 1997; 272(26): 16211 - 16215. [Abstract] [Full Text] [PDF]

				S. Tanaka, T. Ouchi, and H. Hanafusa Downstream of Crk adaptor signaling pathway: Activation of Jun kinase by v-Crk through the guanine nucleotide exchange protein C3G PNAS, March 18, 1997; 94(6): 2356 - 2361. [Abstract] [Full Text] [PDF]

				T. Akagi, T. Shishido, K. Murata, and H. Hanafusa v-Crk activates the phosphoinositide 3-kinase/AKT pathway in transformation PNAS, June 20, 2000; 97(13): 7290 - 7295. [Abstract] [Full Text] [PDF]