title: Dephosphorylation of the focal adhesion protein VASP in vitro and in intact human platelets.
abstract: The focal adhesion protein VASP, a possible link between signal transduction pathways and the microfilament system, is phosphorylated by both cAMP- and cGMP-dependent protein kinases in vitro and in intact cells. Here, the analysis of VASP dephosphorylation by the serine/threonine protein phosphatases (PP) PP1, PP2A, PP2B and PP2C in vitro is reported. The phosphatases differed in their selectivity with respect to the dephosphorylation of individual VASP phosphorylation sites. Incubation of human platelets with okadaic acid, a potent inhibitor of PP1 and PP2A, caused the accumulation of phosphorylated VASP indicating that the phosphorylation status of VASP in intact cells is regulated to a major extent by serine/threonine protein phosphatases. Furthermore, the accumulation of phosphorylated cAMP-dependent protein kinase substrate(s) appears to account for inhibitory effects of okadaic acid on platelet function.
authors.affiliation: Medizinische Universitätsklinik, Klinische Biochemie und Pathobiochemie, Würzburg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Abel
authors.forename: G
authors.initials: G
authors.lastname: Mieskes
authors.forename: U
authors.initials: U
authors.lastname: Walter
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001792:Blood Platelets / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism*; D002417:Cattle; D015815:Cell Adhesion Molecules / Q000187:drug effects / Q000378:metabolism*; D004988:Ethers, Cyclic / Q000494:pharmacology; D006801:Humans; D008969:Molecular Sequence Data; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D013379:Substrate Specificity
chemical_list: D015815:Cell Adhesion Molecules; D004988:Ethers, Cyclic; D010975:Platelet Aggregation Inhibitors; D019319:Okadaic Acid; D017346:Protein Serine-Threonine Kinases; D010749:Phosphoprotein Phosphatases