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Insulin, insulin-like growth factor-I, and platelet-derived growth factor activate extracellular signal-regulated

T Tsakiridis1, E Tsiani, P Lekas

  • 1Clinical Sciences Division, Department of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8.

Biochemical and Biophysical Research Communications
|October 12, 2001
PubMed

Insights

Insulin, IGF-I, and PDGF activate extracellular signal-regulated kinase (ERK) through distinct pathways in L6 myotubes. Insulin uses a Ras-dependent route, PDGF a PKC-dependent route, and IGF-I an independent route.

Area of Science:

  • Cellular signaling pathways
  • Molecular biology
  • Endocrinology

Background:

  • Insulin, IGF-I, and PDGF are key growth factors regulating cellular processes.
  • Extracellular signal-regulated kinase (ERK) is a crucial mediator of cell growth and differentiation.
  • Understanding the specific signaling cascades activated by these growth factors is essential for elucidating cellular responses.

Purpose of the Study:

  • To investigate and delineate the distinct signaling pathways utilized by insulin, IGF-I, and PDGF for ERK activation in L6 myotubes.
  • To identify the roles of Ras, protein kinase C (PKC), and the cytoskeleton in mediating these signaling events.

Main Methods:

  • Utilized specific inhibitors: farnesyl transferase inhibitor (FTPIII) for Ras, cytochalasin D for actin disassembly, bisindolylmaleimide for PKC, wortmannin for PI3K, and PD98059 for MEK.
  • Assessed ERK activation in response to insulin, IGF-I, and PDGF in L6 myotubes under various inhibitory conditions.
  • Investigated the PI3K/Akt/GSK3 pathway activation by these growth factors.

Main Results:

  • Insulin-induced ERK activation was dependent on Ras and the cytoskeleton but independent of PKC.
  • PDGF-induced ERK activation was dependent on PKC but independent of Ras and the cytoskeleton.
  • IGF-I-induced ERK activation was independent of Ras, PKC, and the cytoskeleton.
  • All three growth factors activated the PI3K/Akt/GSK3 pathway via a Ras- and actin-independent mechanism.

Conclusions:

  • ERK activation by insulin, IGF-I, and PDGF is mediated by distinct signaling modules.
  • Insulin utilizes a Ras- and cytoskeleton-dependent pathway.
  • PDGF employs a PKC-dependent pathway.
  • IGF-I activates ERK through a pathway independent of Ras, cytoskeleton, and PKC.

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