The kinase-inactive PDGF β-receptor mediates activation of the MAP kinase cascade via the endogenous PDGF α-receptor in HepG2 cells

Richard Vaillancourt, Anne M. Gardner, Andrius Kazlauskas, Gary L. Johnson

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The PDGF β-receptor in which the active-site lysine in the kinase domain has been mutated to arginine (K634R) lacks intrinsic kinase activity. When expressed in HepG2 cells, the kinase-inactive PDGF β-receptor was tyrosine phosphorylated in response to PDGF-BB. Previously, HepG2 cells were thought to be devoid of PDGF α-receptor primarily due to lack of specific antibody which precluded detection of the PDGF α-receptor. In fact, these cells express low levels of PDGF α-receptor. In HepG2 cells that express the kinase-inactive PDGF β-receptor, PDGF-BB activates the PDGF α-receptors to trans phosphorylate the kinase-inactive PDGF β-receptor in an intermolecular fashion. As a result, stimulation of HepG2 cells that express the kinase-inactive receptor leads to activation of serine/threonine kinases of the MAP kinase cascade which include RAF-1, MEK-1 and p42 MAP kinase. In contrast, the kinase-inactive receptor does not activate any signaling pathways when it is expressed in PC12 cells which do not express the endogenous PDGF α-receptor. Thus, the kinase-inactive K634R PDGF β-receptor is able to enhance PDGF-BB signaling in HepG2 cells that express the PDGF α-receptor.

Original languageEnglish (US)
Pages (from-to)151-159
Number of pages9
JournalOncogene
Volume13
Issue number1
StatePublished - 1996
Externally publishedYes

Fingerprint

Platelet-Derived Growth Factor Receptors
MAP Kinase Signaling System
Hep G2 Cells
Phosphotransferases
Protein-Serine-Threonine Kinases
Mitogen-Activated Protein Kinase Kinases
Mitogen-Activated Protein Kinase 1
PC12 Cells
Lysine
Tyrosine
Arginine
Catalytic Domain

Keywords

  • HepG2 cells
  • MAP kinase
  • PDGF receptor
  • Raf-1

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

The kinase-inactive PDGF β-receptor mediates activation of the MAP kinase cascade via the endogenous PDGF α-receptor in HepG2 cells. / Vaillancourt, Richard; Gardner, Anne M.; Kazlauskas, Andrius; Johnson, Gary L.

In: Oncogene, Vol. 13, No. 1, 1996, p. 151-159.

Research output: Contribution to journalArticle

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