Tyrosine unphosphorylated platelet SHP-1 is a substrate for calpain.
The platelet phosphotyrosine phosphatase (PTP) SHP-1 is tyrosine phosphorylated during thrombin-induced activation. Stimulation of platelets by the ionophore A23187 in the presence of CaCl2 induced a calpain dependent cleavage of SHP-1. SHP-1 proteolysis was undetectable during thrombin-induced stimulation. When SHP-1 was tyrosine phosphorylated by thrombin, further addition of A23187 failed to induce its cleavage. In the presence of tyrphostin to inhibit thrombin-induced SHP-1 tyrosine phosphorylation, SHP-1 was cleaved. Thus, only the tyrosine unphosphorylated form of SHP-1 was a substrate for calpain. A23187 induced the disappearance of all platelet phosphotyrosine proteins and a two-fold increase in PTP activity, both inhibited by pervanadate, a PTP inhibitor, but unaffected by calpeptin, a calpain inhibitor. The data show that SHP-1 is either tyrosine phosphorylated or cleaved by calpain, and suggest that SHP-1 cleavage does not contribute to A23187-induced PTP activity.
Falet
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INSERM U 428, UFR des Sciences Pharmaceutiques et Biologiques, Université René Descartes, Paris Cedex 06, 4 Avenue de l'Observatoire, 75270, France.
Pain
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Rendu
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D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D000001:Calcimycin / Q000494:pharmacology; D002122:Calcium Chloride / Q000494:pharmacology; D002154:Calpain / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D015539:Platelet Activation; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000097:blood* / Q000737:chemistry; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D013379:Substrate Specificity; D013917:Thrombin / Q000494:pharmacology / Q000502:physiology; D014443:Tyrosine; D014638:Vanadates / Q000494:pharmacology; D018909:src Homology Domains
D047908:Intracellular Signaling Peptides and Proteins; C076715:pervanadate; D000001:Calcimycin; D014638:Vanadates; D014443:Tyrosine; 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; D002154:Calpain; D002122:Calcium Chloride