Calpain controls the balance between protein tyrosine kinase and tyrosine phosphatase activities during platelet activation.
Protein phosphorylation was studied during platelet stimulation in two ranges of ionized [Ca2+]. At ionized [Ca2+]i< or = 1 microM, proteins were phosphorylated. At ionized [Ca2+]i > or = 4 microM, 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 [Ca2+] level. Protein tyrosine kinase activity was stimulated at ionized [Ca2+]i < or =1 microM, whereas at ionized [Ca2+]i > or =4 microM, no protein tyrosine kinase activity was observed except in the presence of calpeptin. Thus, the massive tyrosine phosphoprotein disappearance observed at a high ionized [Ca2+]i resulted not only in protein tyrosine phosphatase activation, but also in calpain-induced protein tyrosine kinase inactivation.
Pain
S
S
U428 INSERM, Faculté de Pharmacie, Paris, France.
Monstero-Lastres
A
A
Falet
H
H
Brohard-Bohn
B
B
Fraiz
N
N
Bachelot-Loza
C
C
Cano
E
E
Rendu
F
F
D001798:Blood Proteins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002154:Calpain / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004151:Dipeptides / Q000494:pharmacology; D004789:Enzyme Activation; D006801:Humans; D007476:Ionophores / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D015539:Platelet Activation / Q000502:physiology*; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*
D001798:Blood Proteins; D004151:Dipeptides; D007476:Ionophores; C071482:calpeptin; D011505:Protein-Tyrosine Kinases; D017027:Protein Tyrosine Phosphatases; D002154:Calpain; D002118:Calcium