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.
Edmead
C E
CE
Department of Pharmacology, School of Medical Sciences, University of Bristol, University Walk, Bristol, UK. c.edmead@bristol.ac.uk
Crosby
D A
DA
Southcott
M
M
Poole
A W
AW
D001665:Binding Sites; D001792:Blood Platelets / Q000378:metabolism*; D003432:Cross-Linking Reagents; D006801:Humans; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D008970:Molecular Weight; D010766:Phosphorylation; D015539:Platelet Activation; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism*; D054648:Protein Phosphatase 2; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D013379:Substrate Specificity; D013917:Thrombin / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism; D018909:src Homology Domains; D019061:src-Family Kinases / Q000378:metabolism
D003432:Cross-Linking Reagents; D047908:Intracellular Signaling Peptides and Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D014443:Tyrosine; D019061:src-Family Kinases; D054648:Protein Phosphatase 2; C516724:PTPN11 protein, human; C509249:PTPN6 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D013917:Thrombin