Regulation of glycogen synthase kinase 3 in human platelets: a possible role in platelet function?

FEBS Lett. 2003 Oct 9;553(1-2):173-8. doi: 10.1016/s0014-5793(03)01015-9.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Platelets / drug effects
  • Blood Platelets / enzymology*
  • Blood Platelets / physiology*
  • Collagen / pharmacology
  • Crotalid Venoms / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Glycogen Synthase Kinase 3 / metabolism*
  • Glycogen Synthase Kinase 3 beta
  • Humans
  • Lectins, C-Type*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation / drug effects
  • Platelet Activation / drug effects
  • Platelet Aggregation / drug effects
  • Protein Isoforms / metabolism
  • Serine / metabolism
  • Thrombin / pharmacology

Substances

  • Crotalid Venoms
  • Enzyme Inhibitors
  • Lectins, C-Type
  • Protein Isoforms
  • convulxin
  • Serine
  • Collagen
  • Phosphatidylinositol 3-Kinases
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Glycogen Synthase Kinase 3
  • glycogen synthase kinase 3 alpha
  • Thrombin