Protein phosphatase 1 associates with the integrin αIIb subunit and regulates signaling

被引:49
作者
Vijayan, KV [1 ]
Liu, Y [1 ]
Li, TT [1 ]
Bray, PF [1 ]
机构
[1] Baylor Coll Med, Dept Med, Thrombosis Res Sect, Houston, TX 77030 USA
关键词
D O I
10.1074/jbc.C400239200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Regulation of integrin activation occurs by specific interactions among cytoplasmic proteins and integrin alpha and beta cytoplasmic tails. We report that the catalytic subunit of protein phosphatase 1 (PP1c) constitutively associates with the prototypic integrin alpha(IIb)beta(3) in platelets and in cell lines overexpressing the integrin. PP1c binds directly to the cytoplasmic domain of integrin alpha(IIb) subunit containing a conserved PP1c binding motif (989)KVGF(992). Anchored PP1c is inactive, while thrombin-induced platelet aggregation or fibrinogen-alpha(IIb)beta(3) engagement caused PP1c dissociation and concomitant activation as revealed by dephosphorylation of PP1c substrate, myosin light chain. Inhibition of ligand binding to activated alpha(IIb)beta(3) blocks PP1c dissociation and represses PP1c activation. These studies reveal a previously unrecognized role for integrins whereby the alpha subunit cytoplasmic tail localizes the machinery for initiating and temporally maintaining the regulatory signaling activity of a phosphatase.
引用
收藏
页码:33039 / 33042
页数:4
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