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J. Biol. Chem., Vol. 279, Issue 32, 33039-33042, August 6, 2004

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Protein Phosphatase 1 Associates with the Integrin _IIb Subunit and Regulates Signaling^*

K. Vinod Vijayan, Yan Liu, Tong-Tong Li, and Paul F. Bray

From the Department of Medicine, Baylor College of Medicine, Houston, Texas 77030

Regulation of integrin activation occurs by specific interactions among cytoplasmic proteins and integrin and cytoplasmic tails. We report that the catalytic subunit of protein phosphatase 1 (PP1c) constitutively associates with the prototypic integrin _IIb3 in platelets and in cell lines overexpressing the integrin. PP1c binds directly to the cytoplasmic domain of integrin _IIb subunit containing a conserved PP1c binding motif ⁹⁸⁹KVGF⁹⁹². Anchored PP1c is inactive, while thrombin-induced platelet aggregation or fibrinogen-_IIb3 engagement caused PP1c dissociation and concomitant activation as revealed by dephosphorylation of PP1c substrate, myosin light chain. Inhibition of ligand binding to activated _IIb3 blocks PP1c dissociation and represses PP1c activation. These studies reveal a previously unrecognized role for integrins whereby the subunit cytoplasmic tail localizes the machinery for initiating and temporally maintaining the regulatory signaling activity of a phosphatase.

Received for publication, May 26, 2004 , and in revised form, June 10, 2004.

^* This work was supported by Grants HL57488 and HL65967 from the National Institute of Health, Grant 0435017N from the American Heart Association, and by the Fondren Foundation. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence may be addressed: Thrombosis Research Section, Baylor College of Medicine, One Baylor Plaza, BCM 286, N1319, Houston, TX 77030. Tel.: 713-798-3480; Fax: 713-798-3415; E-mail: pbray{at}bcm.tmc.edu (for P. F. B.) or E-mail: vvijayan{at}bcm.tmc.edu (for K. V. V.).

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