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

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)311-317
Number of pages7
JournalCellular Signalling
Volume9
Issue number3-4
DOIs
Publication statusPublished - May 1997

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

Fingerprint Dive into the research topics of 'Platelet-derived growth factor activates a mammalian Ste20 coupled mitogen-activated protein kinase in airway smooth muscle'. Together they form a unique fingerprint.

  • Cite this