Distinct roles for the α , β and γ1 isoforms of protein phosphatase 1 in the outside-in αIIbβ3 integrin signalling-dependent functions.

Although protein kinases and phosphatases participate in integrin αIIbβ3 signalling, whether integrin functions are regulated by the catalytic subunit of protein phosphatase 1(PP1c)isoforms are unclear. We show that siRNA mediated knockdown of all PP1c isoforms(α, β and γ1)in 293 αIIbβ3 cells decreased adhesion to immobilised fibrinogen and fibrin clot retraction. Selective knockdown of only PP1cγ1 did not alter adhesion or clot retraction, while depletion of PP1cβ decreased both functions.

Cross-talk between serine/threonine protein phosphatase 2A and protein tyrosine phosphatase 1B regulates Src activation and adhesion of integrin αIIbβ3 to fibrinogen.

Integrin α(IIb)β(3) signaling mediated by kinases and phosphatases participate in hemostasis and thrombosis, in part, by supporting stable platelet adhesion. Our previous studies indicate that the genetic manipulation of PP2Acα (α isoform of the catalytic subunit of protein phosphatase 2A) negatively regulate the adhesion of human embryonal kidney 293 cells expressing α(IIb)β(3) to fibrinogen. Here, we demonstrated that small interference RNA (siRNA) mediated knockdown of PP2Acα in 293 α(IIb)β(3) cells led to the dephosphorylation of Src Tyr-529, phosphorylation of Src Tyr-418 and an increased Src kinase activity.

The catalytic subunit of protein phosphatase 1 gamma regulates thrombin-induced murine platelet alpha(IIb)beta(3) function.

Background: Hemostasis and thrombosis are regulated by agonist-induced activation of platelet integrin alpha(IIb)beta(3). Integrin activation, in turn is mediated by cellular signaling via protein kinases and protein phosphatases. Although the catalytic subunit of protein phosphatase 1 (PP1c) interacts with alpha(IIb)beta(3), the role of PP1c in platelet reactivity is unclear.