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, approximately 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.
Mesh Terms:
3T3 Cells, Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Animals, Base Sequence, Binding Sites, Cell Line, Transformed, Cell Transformation, Neoplastic, Cloning, Molecular, DNA, Complementary, GRB2 Adaptor Protein, Hela Cells, Humans, Mice, Molecular Sequence Data, Oncogene Proteins, Phosphorylation, Protein Binding, Proteins, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-abl, Proto-Oncogene Proteins c-crk, Recombinant Fusion Proteins, Sequence Deletion, Yeasts
Genes Dev.
Date: Apr. 01, 1994
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