Incorporation of MAP kinases into the platelet cytoskeleton

Erk1 (p44) and erk2 (p42) mitogen-activated protein (MAP) kinases are activ ated in agonist-stimulated platelets, although their role(s) in the activat ion process is unknown. In the present study, erk1, erk2 and the phosphoryl ated forms of both enzymes became associated with the contractile cytoskele ton in thrombin-stimulated platelets. Enzyme incorporation was accompanied by an increase in MAP kinase activity in the cytoskeleton, which was inhibi ted by PD98059. Pretreatment of the platelets with the arginine-glycine- as partic acid-serine (RGDS) polypeptide enhanced both the cytoskeletal associ ation and the enzyme activity, but cytochalasin D had no significant effect . Platelets from a patient with. Glanzmann's thrombasthenia lack the alpha (IIb)beta (3) integrin and form only a rudimentary cytoskeleton, however, t his cytoskeleton is enriched with both erk1 and erk2. These data suggest ei ther that MAP kinases play a role in cytoskeletal rearrangement or that the cytoskeleton act as a frame to align MAP kinases with substrates in a high ly integrated signal transduction pathway. (C) 2001 Elsevier Science Ltd. A ll rights reserved.