Thrombin-induced association of SHP-2 with multiple tyrosine-phosphorylated proteins in human platelets.

SH2 domain containing phosphatase-2 (SHP-2) has an important regulatory role in a variety of cell types. However, little is known concerning its function in platelets. We show here that, in thrombin-stimulated human platelets, SHP-2 undergoes a time-dependent association with platelet endothelial cell adhesion molecule-1 (PECAM-1) and four low molecular weight phosphoproteins which are attenuated by the Src kinase inhibitor PP1. The low molecular weight proteins, which may be transmembrane proteins, are shown to bind exclusively to the N-terminal SH2 domain of SHP-2 and are therefore possible activators of the phosphatase. In addition, SHP-2 phosphatase activity is shown to be increased following thrombin stimulation or cross-linking of PECAM.