INSULIN-RECEPTOR KINASE PHOSPHORYLATES PROTEIN-TYROSINE-PHOSPHATASE CONTAINING SRC HOMOLOGY 2 REGIONS AND MODULATES ITS PTPASE ACTIVITY IN-VITRO

To clarify the role of protein tyrosine phosphatase (PTPase) containin g a pair of Src homology 2 (SH2) regions upon insulin signaling, we st udied the interactions between the insulin receptor and SH-PTP2 couple d to glutathione-S-transferase. A full length SH-PTP2 was phosphorylat ed by insulin receptor kinase and associated with the insulin receptor in vitro. The N-terminal SH2 domain was more phosphorylated than the other SH2 domain of SH-PTP2. However, both SH2 domains of SH-PTP2 were necessary for association with insulin receptors. Phosphorylation of the SH2 domains of SH-PTP2 resulted in decreased PTPase activities tow ard the phosphorylated insulin receptor. These results indicate that t he insulin receptor can negatively regulate SH-PTP2 activity by means of phosphorylating the SH2 domains. (C) 1994 Academic Press, Inc.