Increased activity of phosphatase PP2A in the presence of the PlA2 polymorphism of αIIbβ3

Huili Wang, Bin Yan, Lisa L. Satterwhite, Qi Ma, Pascal J. Goldschmidt-Clermont

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Polymorphisms in αIIbβ3 are important genetic factors that alter platelet biology and have been associated with susceptibility to thromboembolic disorders. To define the molecular mechanisms that lead to variance in thrombotic diathesis dictated by the β3 polymorphism, we examined regulation of intracellular signaling by αIIbβ3, and studied the effects of a common β subunit PlA2 polymorphism. We found that PP2A regulates αIIbβ3 control of the ERK signaling in a polymorphism specific fashion. In CHO cells, exogenous expression of αIIbβ3 reduced ATP-stimulated ERK phosphorylation and more so for PlA2 than PlA1. Interestingly, reduced level of ERK phosphorylation correlated with an increase in PP2A activity, with higher activity associated with PlA2 than PlA1. We tested the effect of PP2A on αIIbβ3-dependent adhesion, and found that PP2A overexpression increased cell adhesion, while phosphatase inhibitors decreased cell adhesion. We propose that PlA2 alters cell signaling at least in part by increasing β3-associated PP2A activity.

Original languageEnglish (US)
Pages (from-to)72-77
Number of pages6
JournalBiochemical and biophysical research communications
Volume367
Issue number1
DOIs
StatePublished - Feb 29 2008

Keywords

  • Integrin αIIbβ3
  • PlA2 polymorphism
  • PP2A

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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