TY - JOUR
T1 - Increased activity of phosphatase PP2A in the presence of the PlA2 polymorphism of αIIbβ3
AU - Wang, Huili
AU - Yan, Bin
AU - Satterwhite, Lisa L.
AU - Ma, Qi
AU - Goldschmidt-Clermont, Pascal J.
N1 - Funding Information:
The study was supported by NIH award HL73042 (to P.J.G.-C.). The authors are grateful to Soman N. Abraham, Ph.D. Director of Graduate Studies in Pathology, Duke University Medical Center, for his invaluable support and input.
PY - 2008/2/29
Y1 - 2008/2/29
N2 - 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.
AB - 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.
KW - Integrin αIIbβ3
KW - PlA2 polymorphism
KW - PP2A
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U2 - 10.1016/j.bbrc.2007.12.094
DO - 10.1016/j.bbrc.2007.12.094
M3 - Article
C2 - 18155662
AN - SCOPUS:38049043389
VL - 367
SP - 72
EP - 77
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 1
ER -