TYROSINE PHOSPHORYLATION OF AN SH2-CONTAINING PROTEIN-TYROSINE-PHOSPHATASE IS COUPLED TO PLATELET THROMBIN RECEPTOR VIA A PERTUSSIS-TOXIN-SENSITIVE HETEROTRIMERIC G-PROTEIN

SH-STP1 is a protein tyrosine phosphatase (PTP) predominantly expresse d in haematopoietic cells and containing two src homology-2 (SH2) doma ins. Here we report that SH-PTP1 is phosphorylated on both serine and tyrosine residues in response to thrombin or phorbol myristate acetate (PMA), which increased by 60 and 40%, respectively, SH-PTP1 activity, Thrombin-induced phosphorylation of SH-PTP1 is an early signalling ev ent (maximal within 10 s) involving neither integrin signalling, nor c alcium, nor release of ADP or thromboxane A(2). Moreover, in contrast with PMA, the effect of thrombin on the tyrosine phosphorylation of SH -PTP1 was hardly affected by GF109203X, a specific protein kinase C (P KC) inhibitor, Finally, phosphorylation of SH-PTP1 could be provoked i n permeabilized platelets by thrombin or GTP gamma S. This was abolish ed by pertussis toxin, the specificity of this effect being verified w ith the megakaryocytic cell line Dami cell. Our data thus identify SH- PTP1 as an in vivo substrate of a putative protein tyrosine kinase lin ked to the thrombin receptor by a G(i) protein. This might offer some clue to unravel the mechanism of thrombin not only in platelets but al so in nucleated cells, where its mitogenic effect is known to involve pertussis toxin-sensitive G-proteins, tyrosine phosphorylation and the ras pathway.