Phosphoinositide 3-kinase induced activation and cytoskeletal translocation of protein kinase CK2 in protease activated receptor 1-stimulated platelets.
CK2 is a highly conserved protein kinase involved in several cellular events. CK2 is expressed in platelets but its role in platelet activation remains poorly understood. In the present study, we tested the hypothesis that CK2 plays a role in platelet activation, particularly in the PAR1-dependent signal transduction pathway. The effect of CK2 and PI 3-kinase inhibitors on aggregation of platelets, activation of GPIIb/IIIa, activation and translocation of CK2 was examined. Platelets were incubated with the cell permeable CK2 inhibitors, DRB, DMAT and TBB and stimulated with the PAR1-AP (SFLLRNP). CK2 inhibitors showed the specific inhibitory pattern of platelet aggregation, characterized by a primary phase of aggregation followed by progressive disaggregation. CK2 inhibitors suppressed the activation of GPIIb/IIIa. PAR1-AP induced two-fold increase in CK2 activity and stimulated the translocation of CK2 from Triton X-100-soluble to -insoluble fraction. Preincubation of platelets with the PI 3-kinase inhibitor, wortmannin or LY294002, impaired PAR1-AP-induced aggregation of platelets. PAR1-AP-induced increase in CK2 activity and translocation of CK2 were inhibited by these treatments. Taken together, the present study demonstrated, for the first time, that PI 3-kinase-CK2 pathway plays an important role in the mechanism of PAR1-dependent platelet aggregation.
Department of Pediatrics, Mie Chuo Medical Center, Mie, Japan.
Kyoichi
K
Nakanishi
Hidemi
H
Toyoda
Sigeki
S
Tanaka
Hatsumi
H
Yamamoto
Yoshihiro
Y
Komada
Esteban C
EC
Gabazza
Tatsuya
T
Hayashi
Koji
K
Suzuki
Masaru
M
Ido
D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D047390:Casein Kinase II / Q000037:antagonists & inhibitors / Q000097:blood*; D003599:Cytoskeleton / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D047468:Immunoprecipitation; D019869:Phosphatidylinositol 3-Kinases / Q000097:blood*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology*; D010976:Platelet Count; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D044463:Receptor, PAR-1 / Q000097:blood*
D047390:Casein Kinase II; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D047428:Protein Kinase Inhibitors; D044463:Receptor, PAR-1