Thrombin-induced activation of the novel 33-kDa serine/threonine kinase in human platelets.
In order to examine a possible role of protein kinases in the signal transduction of platelet activation, thrombin-stimulated human platelets were analyzed for protein kinase activity with a denaturation/renaturation method. Treatment of platelets with thrombin resulted in a rapid activation of a 33-kDa protein kinase (PK33) using casein as an in vitro substrate. The concentration of thrombin to activate PK33 was proportional to that required to induce platelet aggregation. PK33 was also activated by a thrombin receptor agonist peptide, but not by hirudin-treated or diisopropylphosphate-inactivated thrombin. Phosphoamino acid analysis showed that PK33 is a serine/threonine kinase. Comparative analysis using specific substrate and inhibitors revealed that PK33 is distinct from casein kinase I, casein kinase II, P34cdc2, and mitogen activated protein kinase. These findings suggest that platelet activation mediated by thrombin receptor requires PK33 activation.
Ido
M
M
Department of Molecular Pathobiology, Mie University School of Medicine, Japan.
Ogawa
H
H
Kato
S
S
Hayashi
K
K
Suzuki
K
K
D001792:Blood Platelets / Q000201:enzymology*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000097:blood*; D013917:Thrombin / Q000494:pharmacology*
D017346:Protein Serine-Threonine Kinases; D013917:Thrombin