INSULIN-DEPENDENT TYROSINE PHOSPHORYLATION OF THE TYROSINE INTERNALIZATION MOTIF OF TGN38 CREATES A SPECIFIC SH2 DOMAIN BINDING-SITE

Tyrosine-based motifs are involved in both protein targeting and, via SH2 domain binding, intracellular signalling. To date there has only b een one example of such a motif acting as both an intracellular sortin g signal and SH2 binding determinant, namely that of the T cell costim ulation receptor, CTLA-4. We show that insulin stimulation of cultured rat hepatoma cells results in increased cell surface expression of TG N38. Furthermore, the cytosolic domain of TGN38 can be phosphorylated by the insulin receptor in vitro and tyrosine phosphorylated TGN38 can specifically bind to the SH2 domains of the spleen tyrosine kinase Sy k. These data imply that tyrosine-based motifs may play a broader role than has previously been accepted and could help to integrate traffic king and signalling events. (C) 1997 Federation of European Biochemica l Societies.