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Published April 1, 1994 | Published
Journal Article Open

Abl protein-tyrosine kinase selects the Crk adapter as a substrate using SH3-binding sites


To understand the normal and oncogenic functions of the protein-tyrosine kinase Abl, the yeast two-hybrid system has been used for identifying proteins that interact with it. One interacting protein is Crk-I, an SH3/SH2-containing adapter protein that was originally identified as the oncogenic element in the avian sarcoma virus CT10. Direct interaction between the Crk-I SH3 and Abl at novel, ~10 amino acid sites just carboxy-terminal to the Abl kinase domain occurs in vitro and in mammalian cells. There is a nearby site specific for binding another adapter, Nck, and these sites also bind Grb-2. When bound to Abl, Crk-I was phosphorylated on tyrosine. Thus, the SH3-binding sites on Abl serve as substrate recognition sites for the relatively nonspecific kinase of Abl. In Crk-I-transformed cells, Crk-I associates with endogenous c-Abl and is phosphorylated on tyrosine. The association of Crk and Abl suggests that Abl could play a role in v-Crk and Crk-I transformation and that normal Abl function may be partly mediated through bound adapter molecules.

Additional Information

© 1994 by Cold Spring Harbor Laboratory Press. Received November 19, 1993; revised version accepted February 22, 1994. We thank Dr. R. Brent for kindly providing the yeast two hybrid cloning system, Drs. L. Ron, R. Finley, and E. Golemis for technical advice. Drs. W. Li, A.G. Batzer, and J. Schlessinger for kindly providing the GST-Nck, GST-Grb2, GST/Grb2-N2, and GST/Grb2-2C fusion proteins. We are grateful to Drs. B. Mayer, K. Saksela, G. Cheng, W. Pear, K. Alexandropoulos and other members of D.B.'s laboratory for technical assistance and helpful discussions. This work was supported by a postdoctoral fellowship from the Cancer Research Institute (R.R.), Leukemia Society of America (Z.Y.), and U.S. Public Health Service grant (CA 51462) to D.B. The publication costs of this article were defrayed in part by payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

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August 22, 2023
August 22, 2023