TI  - The SH2 and SH3 domain-containing protein <prot>GRB2</prot> links receptor tyrosine
      kinases to ras signaling.
PG  - 431-42
AB  - A cDNA clone encoding a novel, widely expressed protein (called <prot>growth
      factor receptor-bound protein 2</prot> or <prot>GRB2</prot>) containing one src homology 2
      (SH2) domain and two SH3 domains was isolated. Immunoblotting experiments
      indicate that   <prot>GRB2</prot>   associates with  tyrosine-phosphorylated  epidermal
      growth factor receptors (EGFRs)  and  platelet-derived growth factor
      receptors (PDGFRs)  via its SH2 domain. Interestingly, <prot>GRB2</prot> 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 <prot>GRB2</prot>
      is also a component of ras signaling in mammalian cells, microinjection
      studies were performed. While injection of <prot>GRB2</prot> or <prot>H-ras</prot> proteins alone
      into quiescent rat fibroblasts did not have mitogenic effect,
      microinjection of <prot>GRB2</prot> together with <prot>H-ras</prot> protein stimulated DNA
      synthesis. These results suggest that <prot>GRB2</prot>/<prot>sem-5</prot> plays a crucial role in a
      highly conserved mechanism for growth factor control of ras signaling.
AD  - Department of Pharmacology, New York University Medical Center, New York
