Abstract
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 alphaIIbbeta3 in platelets and in cell lines overexpressing the integrin. PP1c binds directly to the cytoplasmic domain of integrin alphaIIb subunit containing a conserved PP1c binding motif 989KVGF992. Anchored PP1c is inactive, while thrombin-induced platelet aggregation or fibrinogen-alphaIIbbeta3 engagement caused PP1c dissociation and concomitant activation as revealed by dephosphorylation of PP1c substrate, myosin light chain. Inhibition of ligand binding to activated alphaIIbbeta3 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.
Highlights
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
Unlike the situation with kinases, only serine/threonine protein phosphatase PP2A has been reported to associate with integrin 1 [10], while only tyrosine phosphatase SHP-2 is known to associate with 3 [11]
Summary
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. Phosphatases play an essential role in dampening platelet phosphorylation events, and serine/threonine dephosphorylation of cytoskeletal proteins like cofilin, talin, and vasodilatorstimulated phosphoprotein correlates with platelet activation [7,8,9].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
