The SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine kinases to ras signaling

作者：Eve Judith Lowenstein, Roger J. Daly, Andreas Batzer, W. Li, Ben L. Margolis, Reiner Lammers, Axel Ullrich, Edward Y. Skolnik, Dafna Bar‐Sagi, Joseph Schlessinger · 发表于：Cell · 年份：1992 · DOI：10.1016/0092-8674(92)90167-b · 被引用次数：1666 · 研究领域：Genetics, Aging, and Longevity in Model Organisms、FOXO transcription factor regulation、Protein Kinase Regulation and GTPase Signaling

A cDNA clone encoding a novel, widely expressed protein (called growth factor receptor-bound protein 2 or GRB2) containing one src homology 2 (SH2) domain and two SH3 domains was isolated. Immunoblotting experiments indicate that GRB2 associates with tyrosine-phosphorylated epidermal growth factor receptors (EGFRs) and platelet-derived growth factor receptors (PDGFRs) via its SH2 domain. Interestingly, GRB2 exhibits striking structural and functional homology to the C. elegans protein sem-5. It has been shown that sem-5 and two other genes called let-23 (EGFR like) and let-60 (ras like) lie along the same signal transduction pathway controlling C. elegans vulval induction. To examine whether GRB2 is also a component of ras signaling in mammalian cells, microinjection studies were performed. While injection of GRB2 or H-ras proteins alone into quiescent rat fibroblasts did not have mitogenic effect, microinjection of GRB2 together with H-ras protein stimulated DNA synthesis. These results suggest that GRB2/sem-5 plays a crucial role in a highly conserved mechanism for growth factor control of ras signaling.