P38 mitogen-activated protein kinase dephosphorylation is regulated by protein phosphatase 2A in human platelets activated by collagen.

Collagen and the cross-linked collagen-related peptide (CRP-XL) each induced platelet p38 mitogen-activated protein kinase (p38) phosphorylation after 2 min. Subsequent dephosphorylation occurred in platelets activated with collagen, but not with CRP-XL, demonstrating glycoprotein VI-independent regulation of p38. Okadaic acid and fostriecin, inhibitors specific for protein phosphatase 2A (PP2A), blocked p38 dephosphorylation, and PP2A co-immunoprecipitated with phospho-p38. In addition, use of phenylarsine oxide suggested that tyrosine phosphatases and PP2A may act in concert to dephosphorylate p38. Finally, regulation of p38 in collagen-stimulated Glanzmann's platelets was indistinguishable from that in normal platelets, showing that p38 regulation is independent of integrin alphaIIbbeta3.