Calpain controls the balance between protein tyrosine kinase and tyrosine phosphatase activities during platelet activation

• Published in: FEBS letters Vol. 453; no. 1; pp. 119 - 123
• Main Authors: Pain, Sabine, Monstero-Lastres, Alfonso, Falet, Hervé, Brohard-Bohn, Brigitte, Fraiz, Nuria, Bachelot-Loza, Christilla, Cano, Ernesto, Rendu, Francine
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 18.06.1999
• Subjects: [Ca2+]i, ionized cytosolic calcium; Blood Proteins - metabolism; Calcium; Calcium - metabolism; Calpain; Calpain - antagonists & inhibitors; Calpain - metabolism; Dipeptides - pharmacology; Enzyme Activation; Humans; Ionophores - pharmacology; OA, okadaic acid; PAGE, polyacrylamide gel electrophoresis; Phosphorylation; Phosphorylation - drug effects; Platelet activation; Platelet Activation - physiology; Protein Tyrosine Phosphatases - antagonists & inhibitors; Protein Tyrosine Phosphatases - metabolism; Protein-Tyrosine Kinases - metabolism; PTK, protein tyrosine kinase; PTP, protein tyrosine phosphatase; SDS, sodium dodecyl sulfate; OA, okadaic acid; Phosphorylation; Platelet activation; Calcium; PTK, protein tyrosine kinase; PAGE, polyacrylamide gel electrophoresis; Calpain; [Ca 2+] i, ionized cytosolic calcium; SDS, sodium dodecyl sulfate; PTP, protein tyrosine phosphatase
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(99)00698-5

Protein phosphorylation was studied during platelet stimulation in two ranges of ionized [Ca 2+]. At ionized [Ca 2+] i≤1 μM, proteins were phosphorylated. At ionized [Ca 2+] i≥4 μM, phosphoproteins disappeared. Protein dephosphorylation was prevented by the combined action of calpeptin and phosphatase inhibitors. Protein tyrosine phosphatase activity was stimulated regardless of the ionized [Ca 2+] i level. Protein tyrosine kinase activity was stimulated at ionized [Ca 2+] i≤1 μM, whereas at ionized [Ca 2+] i≥4 μM, no protein tyrosine kinase activity was observed except in the presence of calpeptin. Thus, the massive tyrosine phosphoprotein disappearance observed at a high ionized [Ca 2+] i resulted not only in protein tyrosine phosphatase activation, but also in calpain-induced protein tyrosine kinase inactivation.