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PI3K is required for insulin-stimulated but not EGF-stimulated ERK1/2 activation

Authors
Journal
European Journal of Cell Biology
0171-9335
Publisher
Elsevier
Publication Date
Volume
85
Issue
5
Identifiers
DOI: 10.1016/j.ejcb.2005.11.005
Keywords
  • Extracellular Signal-Regulated Kinase 1 And 2
  • Phosphatidylinositol 3-Kinase
  • Insulin
  • Epidermal Growth Factor
  • Ras
  • Akt
  • Wortmannin
  • Ly294002
  • Protein Kinase C
  • Phorbol 12-Myristate 13-Acetate
Disciplines
  • Biology

Abstract

Abstract The Ras/Raf/extracellular signal-regulated kinase 1 and 2 (ERK1/2) signaling pathway is known to cross-talk with other signaling pathways, including phosphatidylinositol 3-kinase (PI3K)/Akt pathway. However, the role of PI3K in ERK-1/2 activation induced by tyrosine kinase receptors was not fully understood. Here, we report that two structurally distinct PI3K inhibitors, wortmannin and LY294002, inhibited insulin-induced activation of ERK1/2 but had no effect on EGF-induced activation of ERK1/2 in hepatocellular carcinoma BEL-7402 and SMMC-7721 cells, breast cancer MCF-7 cells, and prostate cancer LNCaP cells. Although protein kinase C could act as a mediator between PI3K and ERK1/2, protein kinase C inhibitor chelerythrine chloride did not inhibit insulin-induced ERK1/2 activation. Both insulin- and EGF-induced ERK1/2 activation are strictly dependent on Ras activation, however, wortmannin only inhibited insulin-induced, but not EGF-induced Ras activation. These results indicate that PI3K plays different roles in the activation of Ras/ERK1/2 signaling by insulin and EGF, and that insulin-stimulated, but not EGF-stimulated, ERK1/2 and Akt signalings diverge at PI3K.

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