Related Experiment Video
Updated: Sep 27, 2026

Phospholipid Mediator Induced Transformation in Three-Dimensional Cultures
Published on: July 27, 2022
Platelet-derived growth factor induces phosphatidylinositol 3-kinase release from the middle T-pp60c-src complex and
1Ludwig Institute for Cancer Research, Melbourne Tumour Biology Branch, Royal Melbourne Hospital, Victoria, Australia.
Abstract:
Both platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) induce mitogenesis in normal rat kidney (NRK) fibroblasts transformed by the polyoma virus middle T (pmt) oncogene. In unstimulated pmt-NRK cells phosphatidylinositol 3-kinase forms a complex with the middle T protein and pp60c-src. PDGF treatment causes a release of phosphatidylinositol 3-kinase activity from the complex and a simultaneous increase in activity associated with the PDGF receptor. In contrast after treatment with EGF the majority of phosphatidylinositol 3-kinase activity remains associated with the middle T-pp60c-src complex. Proliferation of NRK fibroblasts transformed by the v-src oncogene is already maximal, and no further stimulation is observed with either PDGF or EGF. Neither growth factor induces dissociation of the complex between phosphatidylinositol 3-kinase and pp60v-src. These observations suggest that the complex between phosphatidylinositol 3-kinase, the middle T protein and pp60c-src is dissociable, and that phosphatidylinositol 3-kinase plays different roles in mitogenic signal transduction by the PDGF and EGF receptors.
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.
Related Concept Videos
What are Second Messengers?
Phosphoinositides and PIPs
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
Amplifying Signals via Second Messengers
Receptor Tyrosine Kinases
PI3K/mTOR/AKT Signaling Pathway
IP3/DAG Signaling Pathway

