JNK-SAPK activation by platelet-derived growth factor in A431 cells requires both the phospholipase C-γ and the phosphatidylinositol 3-kinase signaling pathways of the receptor

Zerihun Assefa, Mindaugas Valius, T. Vántus, Patrizia Agostinis, Wilfried Merlevede, Jackie R. Vandenheede

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Wild-type or mutant βPDGF receptors were introduced into A431 cells that lack endogenous PDGF receptors. PDGF stimulates JNK1 activity in a dose- and time-dependent manner in cells expressing the wild-type receptor. A receptor mutant lacking all the binding sites for SHP-2 GAP, PI3K, and PLC-γ fails to activate JNK1. Receptor mutants with no binding site for either SHP-2 or GAP can fully activate JNK1 but those which do not bind either PI3K or PLC-γ are unable to induce JNK1 activation. PDGF-dependent JNK1 activation was reduced upon cell pretreatment with wortmannin or GF109203X and is completely abrogated by chronic PMA stimulation. Altogether, these results indicate that PDGF activates JNK1 through a pathway that involves both PI3K and PLC-γ and subsequent activation of protein kinase C.

Original languageEnglish
Pages (from-to)641-645
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume261
Issue number3
DOIs
Publication statusPublished - Aug 11 1999

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Phosphatidylinositol 3-Kinase
Platelet-Derived Growth Factor
Type C Phospholipases
Programmable logic controllers
Phosphatidylinositol 3-Kinases
Platelet-Derived Growth Factor Receptors
Chemical activation
Binding Sites
Protein Kinase C
Cells

Keywords

  • JNK
  • PDGF
  • PI3K
  • PLC-γ
  • Tyrosine kinase

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

JNK-SAPK activation by platelet-derived growth factor in A431 cells requires both the phospholipase C-γ and the phosphatidylinositol 3-kinase signaling pathways of the receptor. / Assefa, Zerihun; Valius, Mindaugas; Vántus, T.; Agostinis, Patrizia; Merlevede, Wilfried; Vandenheede, Jackie R.

In: Biochemical and Biophysical Research Communications, Vol. 261, No. 3, 11.08.1999, p. 641-645.

Research output: Contribution to journalArticle

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