THE TRANSMEMBRANE PROTEIN-TYROSINE-PHOSPHATASE-ALPHA DEPHOSPHORYLATESTHE INSULIN-RECEPTOR IN INTACT-CELLS

Protein tyrosine phosphatases (PTPs) are key regulators in a variety o f signal transduction processes. However, substrates for most PTPs hav e not been determined. In a previous report, we demonstrated that in a transient expression system the intracellular phosphatases PTPs 1B an d TC preferentially dephosphorylated the precursor form of several rec eptor tyrosine kinases. In this paper we show that the dephosphorylati on of kinase precursors is a specific feature of PTPs 1B and TC that i s not shared by two other intracellular PTPs, PTPH1 or SHP-1. By contr ast, the receptor phosphatase PTP alpha preferentially dephosphorylate d the beta-subunit of the insulin receptor localized on the cell surfa ce. The insulin receptor was a better substrate for PTP alpha than for other receptor type PTPs. We conclude that the intracellular PTPs 1B and TC regulate the autophosphorylation of receptor tyrosine kinases d uring their posttranslational processing while receptor type PTPs regu late the mature, cell surface localized receptor tyrosine kinases. (C) 1997 Federation of European Biochemical Societies.