Incorporation of map kinases into the platelet cytoskeleton.
Erk1 (p44) and erk2 (p42) mitogen-activated protein (MAP) kinases are activated in agonist-stimulated platelets, although their role(s) in the activation process is unknown. In the present study, erk1, erk2 and the phosphorylated forms of both enzymes became associated with the contractile cytoskeleton in thrombin-stimulated platelets. Enzyme incorporation was accompanied by an increase in MAP kinase activity in the cytoskeleton, which was inhibited by PD98059. Pretreatment of the platelets with the arginine-glycine-aspartic acid-serine (RGDS) polypeptide enhanced both the cytoskeletal association 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, this cytoskeleton is enriched with both erk1 and erk2. These data suggest either 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 highly integrated signal transduction pathway.
McNicol
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A
Department of Oral Biology, University of Manitoba, R3E 0W2, Winnipeg, Manitoba, Canada. mcnicol@ms.umanitoba.ca
Shibou
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TS
Pampolina
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C
Israels
S J
SJ
D000328:Adult; D001792:Blood Platelets / Q000201:enzymology* / Q000648:ultrastructure; D015638:Cytochalasin D / Q000494:pharmacology; D003599:Cytoskeleton / Q000201:enzymology* / Q000378:metabolism / Q000502:physiology; D005260:Female; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D010766:Phosphorylation; D015539:Platelet Activation / Q000187:drug effects; D013915:Thrombasthenia / Q000097:blood; D013917:Thrombin / Q000494:pharmacology
D009842:Oligopeptides; D015638:Cytochalasin D; C047981:arginyl-glycyl-aspartic acid; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D013917:Thrombin