Platelet-derived growth factor induces phosphatidylinositol 3-kinase release from the middle T-pp60c-src complex and

Q X Zhang1, G S Baldwin

  • 1Ludwig Institute for Cancer Research, Melbourne Tumour Biology Branch, Royal Melbourne Hospital, Victoria, Australia.

Insights

Platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) trigger cell growth differently in polyoma virus middle T oncogene-transformed cells. Phosphatidylinositol 3-kinase behaves distinctly upon PDGF versus EGF stimulation, impacting cell signaling pathways.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Oncology

Background:

  • Polyoma virus middle T (pmt) oncogene transforms normal rat kidney (NRK) fibroblasts, rendering them responsive to mitogenic factors.
  • Platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) are key regulators of cell proliferation.
  • Phosphatidylinositol 3-kinase (PI3K) is a critical enzyme in cellular signaling pathways.

Purpose of the Study:

  • To investigate the differential roles of PDGF and EGF in activating mitogenic signaling pathways in pmt-NRK cells.
  • To elucidate the behavior of phosphatidylinositol 3-kinase (PI3K) in response to PDGF and EGF stimulation in the context of specific oncogene transformations.

Main Methods:

  • Utilized normal rat kidney (NRK) fibroblasts transformed with the polyoma virus middle T (pmt) oncogene.
  • Stimulated cells with either PDGF or EGF and analyzed the association of PI3K with signaling complexes.
  • Examined the impact of v-src oncogene transformation on growth factor-induced signaling.

Main Results:

  • In pmt-NRK cells, PDGF treatment dissociates PI3K from the middle T-pp60c-src complex, increasing PI3K activity at the PDGF receptor.
  • EGF treatment, however, maintains PI3K activity associated with the middle T-pp60c-src complex in pmt-NRK cells.
  • In v-src transformed NRK cells, neither PDGF nor EGF induced further proliferation or dissociation of the PI3K-pp60v-src complex.

Conclusions:

  • The complex involving PI3K, middle T protein, and pp60c-src is dissociable, with distinct PI3K dynamics upon PDGF versus EGF stimulation.
  • PI3K plays differential roles in mitogenic signal transduction mediated by PDGF and EGF receptors.
  • Oncogene context significantly influences growth factor signaling pathways and PI3K involvement.

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