title: P38 mitogen-activated protein kinase dephosphorylation is regulated by protein phosphatase 2A in human platelets activated by collagen.
abstract: 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.
authors.affiliation: Department of Biochemistry, University of Cambridge, Building 0, Downing Site, UK.
authors.forename: Pavithra
authors.initials: P
authors.lastname: Sundaresan
authors.forename: Richard W
authors.initials: RW
authors.lastname: Farndale
mesh_terms: D000475:Alkenes / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002352:Carrier Proteins / Q000494:pharmacology; D002417:Cattle; D003094:Collagen / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D020928:Mitogen-Activated Protein Kinases / Q000097:blood*; D019319:Okadaic Acid / Q000494:pharmacology; D010455:Peptides; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000097:blood*; D010766:Phosphorylation; D015539:Platelet Activation / Q000187:drug effects; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D011090:Polyenes; D054648:Protein Phosphatase 2; D011753:Pyrones; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D000475:Alkenes; D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D010455:Peptides; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011090:Polyenes; D011753:Pyrones; C435908:collagen-related peptide; D019319:Okadaic Acid; D003094:Collagen; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; C040313:fostriecin