Falet H, Pain S, Rendu F
INSERM U 428, UFR des Sciences Pharmaceutiques et Biologiques, Université René Descartes, Paris Cedex 06, 4 Avenue de l'Observatoire, 75270, France.
Biochem Biophys Res Commun. 1998 Nov 9;252(1):51-5. doi: 10.1006/bbrc.1998.9593.
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.
血小板磷酸酪氨酸磷酸酶（PTP）SHP - 1在凝血酶诱导的激活过程中发生酪氨酸磷酸化。在氯化钙存在的情况下，离子载体A23187刺激血小板会诱导SHP - 1发生钙蛋白酶依赖性裂解。在凝血酶诱导的刺激过程中未检测到SHP - 1的蛋白水解。当SHP - 1被凝血酶酪氨酸磷酸化后，进一步添加A23187未能诱导其裂解。在存在 tyrphostin抑制凝血酶诱导的SHP - 1酪氨酸磷酸化的情况下，SHP - 1发生了裂解。因此，只有酪氨酸未磷酸化形式的SHP - 1是钙蛋白酶的底物。A23187诱导所有血小板磷酸酪氨酸蛋白消失，并且使PTP活性增加两倍，这两种情况均被PTP抑制剂过氧钒酸盐抑制，但不受钙蛋白酶抑制剂钙肽素的影响。数据表明SHP - 1要么被酪氨酸磷酸化，要么被钙蛋白酶裂解，并且表明SHP - 1裂解对A23187诱导的PTP活性没有贡献。
