Distinct roles for the ? , ? and ?1 isoforms of protein phosphatase 1 in the outside-in ?IIb?3 integrin signalling-dependent functions.

ABSTRACT: Although protein kinases and phosphatases participate in integrin ?IIb?3 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(?, ? and ?1)in 293 ?IIb?3 cells decreased adhesion to immobilised fibrinogen and fibrin clot retraction. Selective knockdown of only PP1c?1 did not alter adhesion or clot retraction, while depletion of PP1c? decreased both functions. Unexpectedly, knockdown of PP1c? enhanced ?IIb?3 adhesion to fibrinogen and clot retraction. Protein interaction studies revealed that all PP1c isoforms can interact with the integrin ?IIb subunit. Phospho-profiling studies revealed an enhanced activation of mitogen-activated protein kinase (MAPK) p38 in the PP1c? depleted cells. Enhanced adhesive phenotype displayed by the PP1c?-depleted 293 ?IIb?3 cells was blocked by pharmacological inhibition of p38. Conversely, the decreased adhesion of PP1c? overexpressing cells was rescued by the expression of constitutively active p38? or p38?. Thus, PP1c isoforms have distinct contribution to the outside-in ?IIb?3 signalling-dependent functions in 293 ?IIb?3 cells. Moreover, PP1c? negatively regulates integrin function by suppressing the p38 pathway.

SUBMITTER: Alrehani N 

PROVIDER: S-EPMC3749075 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature