APS (adapter protein with a PH and SH2 domain) is the newest member of a fa
mily of tyrosine kinase adapter proteins including SH2-B and Lnk. We previo
usly identified SH2-B as an insulin-receptor-binding protein and substrate
[Kotani, Wilden and Pillay (1998) Biochem J. 335, 103-109]. Here we show th
at APS interacts with the insulin receptor kinase activation loop through i
ts SH2 domain and insulin stimulates the tyrosine-phosphorylation of APS. F
urthermore, the phosphorylation activation-loop tyrosine residues 1158 and
1162 are required for this interaction.