Multiple Grb2-protein complexes in human cancer cells.

Grb2 is an SH2/SH3 domain-containing adaptor protein that links receptor tyrosine kinases to the ras signaling pathway. The Grb2-SH2 domain binds phosphotyrosine sequences on activated tyrosine kinases, and one target of the SH3 domains is the ras-nucleotide-exchange factor Sos1. We have examined Grb2-protein interactions in human cancer cells that over-express ...
the receptor tyrosine kinase erbB2. Our results show that the 2 Grb2-SH3 domains complex with Sos1, dynamin and at least 4 other proteins (p228, p140, p55, p28) in these cells. The 2 Grb2-SH3 domains bind these proteins differently, with the N-terminal SH3 domain interacting preferentially with p228, Sos1, p140 and dynamin. The C-terminal SH3 domain has higher affinity toward p28. The Grb2-SH3 domain interactions appear to be similar in erbB2 over-expressing breast, ovarian and lung cancer cells. Also, the major tyrosine-phosphorylated proteins that associate with Grb2 in erbB2 over-expressing cancer cells appear to be erbB2 and Shc. The multiple Grb2-SH3 domain interactions in these cells may mediate novel cellular functions.
Mesh Terms:
3T3 Cells, Adaptor Proteins, Signal Transducing, Animals, GRB2 Adaptor Protein, Genes, ras, Humans, Macromolecular Substances, Mice, Neoplasm Proteins, Neoplasms, Phosphotyrosine, Protein Binding, Proteins, Receptor, erbB-2, Transfection, Tumor Cells, Cultured, src Homology Domains
Int. J. Cancer
Date: Jan. 17, 1997
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