First Author | Wang J | Year | 1998 |
Journal | J Biol Chem | Volume | 273 |
Issue | 6 | Pages | 3136-9 |
PubMed ID | 9452421 | Mgi Jnum | J:45715 |
Mgi Id | MGI:1195870 | Doi | 10.1074/jbc.273.6.3136 |
Citation | Wang J, et al. (1998) Insulin-like growth factor-I receptor and insulin receptor association with a Src homology-2 domain-containing putative adapter. J Biol Chem 273(6):3136-9 |
abstractText | Insulin receptor (IR) and the related insulin-like growth factor-I (IGF-I) receptor (IGF-IR) mediate a variety of metabolic and mitogenic cellular responses, some of which may involve unidentified receptor targets. A Src homology-2 (SH2) domain-coding region of a mouse protein was cloned based on its interaction with IR. It was designated mSH2-B based on its high similarity to an earlier reported rat sequence SH2-B. A role of mSH2-B in IGF-I and insulin action was suggested by the interaction of the SH2 domain with activated IGF-IR and IR catalytic fragments but not with an inactive IR catalytic fragment in the yeast two-hybrid system in vivo and by the hormone-dependent association of a glutathione S-transferase (GST) SH2 domain fusion protein of mSH2-B with both receptors in cell extracts. A comparison of IGF-IR and IR mutants lacking individual Tyr autophosphorylation sites for association with GST mSH2-B showed that homologous juxtamembrane (IR960/IGF-IR950) and C-terminal (IR1322/IGF-IR1316) receptor motifs were required. Synthetic phosphopeptides representing IR960 and IR1322 competed for GST mSH2-B binding to the receptor, suggesting that both motifs participate in the association with mSH2-B. Antibodies raised against GST mSH2-B identified a cellular protein of 92 kDa that was not found to be phosphorylated on Tyr. It co-immunoprecipitated with IGF-IR or IR, which was strictly dependent on receptor activation. IR and IGF-IR Tyr phosphorylation motifs were not identified in the complete SH2-B primary structure, suggesting that it may participate as an adapter rather than a substrate in the IGF-I and insulin signaling pathways. |