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Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes
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Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes

Published on: September 28, 2018

PDGF-BB-mediated activation of p42(MAPK) is independent of PDGF beta-receptor tyrosine phosphorylation

N J Cartel1, J Liu, J Wang

  • 1Canadian Institutes of Health Research Group in Lung Development, Programme in Lung Biology, Research Institute, Toronto, Ontario, Canada.

American Journal of Physiology. Lung Cellular and Molecular Physiology
|September 15, 2001
PubMed

Insights

Platelet-derived growth factor (PDGF)-BB activates mitogen-activated protein kinase (MAPK) signaling. This activation requires the PDGF beta-receptor (PDGFR-beta) but is independent of PDGFR-beta tyrosine phosphorylation and glycosaminoglycan synthesis.

Area of Science:

  • Cellular signaling pathways
  • Molecular biology
  • Receptor tyrosine kinases

Background:

  • Mitogen-activated protein kinase (MAPK) is crucial for downstream signaling events.
  • Platelet-derived growth factor (PDGF)-BB stimulation activates MAPK.
  • The precise mechanisms of PDGF-BB-induced MAPK activation are not fully understood.

Purpose of the Study:

  • To investigate the role of PDGF-BB in activating MAPK.
  • To determine the specific components and signaling pathways involved in PDGF-BB-mediated MAPK activation.
  • To elucidate the relationship between PDGFR-beta, its tyrosine phosphorylation, and MAPK activation.

Main Methods:

  • Stimulation of cells with PDGF-BB.
  • Assessing p42(MAPK) activity and phosphorylation.
  • Utilizing chemical inhibitors for various kinases (Janus kinase, phosphatidylinositol 3-kinase, Src kinase).
  • Employing dominant-negative constructs for RHAMM and PDGFR-beta variants.

Main Results:

  • PDGF-BB stimulation led to a peak in p42(MAPK) activity at 60 minutes.
  • p42(MAPK) activation was not directly involved in glycosaminoglycan synthesis.
  • PDGF-BB activated MAPKK2 but not MAPKK1 or Raf-1.
  • Inhibition of various kinases or PDGFR-beta tyrosine phosphorylation did not prevent p42(MAPK) activation.
  • A dominant-negative PDGFR-beta lacking the signaling domain abrogated p42(MAPK) activity.

Conclusions:

  • PDGF-BB-mediated p42(MAPK) activation is dependent on the PDGFR-beta.
  • This activation is independent of PDGFR-beta tyrosine phosphorylation.
  • The findings clarify a specific aspect of PDGF signaling and MAPK activation pathways.

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