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Platelet-derived growth factor activates a mammalian Ste20 coupled mitogen-activated protein kinase in airway smooth muscle

Pyne, N J and Pyne, S (1997) Platelet-derived growth factor activates a mammalian Ste20 coupled mitogen-activated protein kinase in airway smooth muscle. Cellular Signalling, 9 (3-4). pp. 311-317. ISSN 0898-6568

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Abstract

We have investigated the mechanisms regulating p38MAPK in airway smooth muscle cells. Incubation of cells with platelet-derived growth factor (PDGF) stimulated MAPKA kinase-2 activity, a kinase immediately down-stream of P38MAPK. Preincubation of the cells with forskolin (10 microM), which stimulated a 20-fold increase in intracellular cAMP formation, inhibited this response. An antibody raised against subdomain VI of yeast Ste20 kinase co-immunoprecipitated p38MAPK from cell lysates. The immunoprecipitated kinase(s) was shown to catalyse the phosphorylation of myelin basic protein (MBP) and to activate purified MAPKAP kinase-2. Incubation of cells with PDGF did not increase the amount of p38MAPK isolated in the anti-Ste20 immunoprecipitate. However, the kinase phosphorylated MBP and stimulated purified MAPKAP kinase-2 activity more effectively than kinase from control cells. The preincubation of cells with forskolin (10 microM) reduced the amount of P38MAPK in the immunoprecipitate and this correlated with a decrease in kinase activity. We conclude the PDGF induces the activation of p38MAPK, whereas forskolin elicits its dissociation from the complex with Ste20. Therefore, Ste20/p38MAPK may form part of a signal transduction pathway linked to activation of MAPKAP kinase-2 in ASM cells.

Item type: Article
ID code: 34934
Keywords: animals, calcium-calmodulin-dependent protein kinases, cells, cultured, enzyme activation, guinea pigs, intracellular signaling peptides and proteins, mitogen-activated protein kinases, muscle, smooth, phosphorylation, platelet-derived growth factor, precipitin tests, protein-serine-threonine kinases, rabbits, saccharomyces cerevisiae proteins, tyrosine, p38 mitogen-activated protein kinases, Pharmacy and materia medica
Subjects: Medicine > Pharmacy and materia medica
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Related URLs:
    Depositing user: Pure Administrator
    Date Deposited: 15 Nov 2011 15:10
    Last modified: 12 Mar 2012 11:37
    URI: http://strathprints.strath.ac.uk/id/eprint/34934

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