Microfilament assembly is required for anti-IgM dependent MAPK and p90rsk activation in human B lymphocytes.
Mitogen-activated protein kinases (MAPK) are important mediators of signal transduction from the cell surface to the nucleus. These MAPK pathways serve different receptor-mediated signaling pathways leading to dual phosphorylation on serine/threonine and tyrosine residues. The mechanisms linking cytoplasmic MAPK activation to later events is still unclear. In this study we demonstrate that the microfilament system has an active role in MAPK activation. Cross-linking of surface IgM or direct activation of PKC with PMA resulted in time and concentration-dependent increases in F-actin content, MAPK (p42erk-2) activation, and phosphorylation of p90rsk. Pretreatment of the B cells with cytochalasin D or botulinum C2 toxin, microfilament-disrupting agents, prevented the increases in F-actin content as well as MAPK and p90rsk activation. These data indicate a role for the microfilament system in the complex and divergent functions of MAPK.
Melamed
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Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206, USA.
Franklin
R A
RA
Gelfand
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EW
D008841:Actin Cytoskeleton / Q000502:physiology*; D000199:Actins / Q000187:drug effects / Q000378:metabolism*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D015153:Blotting, Western; D001905:Botulinum Toxins / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002478:Cells, Cultured; D015638:Cytochalasin D / Q000494:pharmacology; D004789:Enzyme Activation; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology* / Q000494:pharmacology; D007700:Kinetics; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D019893:Ribosomal Protein S6 Kinases; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000199:Actins; D007075:Immunoglobulin M; D015638:Cytochalasin D; D017346:Protein Serine-Threonine Kinases; D019893:Ribosomal Protein S6 Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D001905:Botulinum Toxins; D013755:Tetradecanoylphorbol Acetate