Regulation of glycogen synthase kinase 3 in human platelets: a possible role in platelet function?
In this study we show that both glycogen synthase kinase 3 (GSK3) isoforms, GSK3alpha and GSK3beta, are present in human platelets and are phosphorylated on Ser(21) and Ser(9), respectively, in platelets stimulated with collagen, convulxin and thrombin. Phosphorylation of GSK3alpha/beta was dependent on phosphoinositide 3-kinase (PI3K) activity and independent of platelet aggregation, and correlated with a decrease in GSK3 activity that was preserved by pre-incubating platelets with PI3K inhibitor LY294002. Three structurally distinct GSK3 inhibitors, lithium, SB415286 and TDZD-8, were found to inhibit platelet aggregation. This implicates GSK3 as a potential regulator of platelet function.
Barry
Fiona A
FA
School of Animal and Microbial Sciences, The University of Reading, Whiteknights, PO Box 228 RG6 6AJ, Reading, UK.
Graham
Gwenda J
GJ
Fry
Michael J
MJ
Gibbins
Jonathan M
JM
D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology*; D003094:Collagen / Q000494:pharmacology; D003435:Crotalid Venoms / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D037181:Lectins, C-Type; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D020033:Protein Isoforms / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology
D003435:Crotalid Venoms; D004791:Enzyme Inhibitors; D037181:Lectins, C-Type; D020033:Protein Isoforms; C028890:convulxin; D012694:Serine; D003094:Collagen; D019869:Phosphatidylinositol 3-Kinases; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; C448021:glycogen synthase kinase 3 alpha; D013917:Thrombin