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.
CITATION STYLE
Sastry, L., Cao, T., & King, C. R. (1997). Multiple Grb2-protein complexes in human cancer cells. International Journal of Cancer, 70(2), 208–213. https://doi.org/10.1002/(SICI)1097-0215(19970117)70:2<208::AID-IJC12>3.0.CO;2-E
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