Related Experiment Videos
Cross-talk between the proto-oncogenes Met and Ron
A Follenzi1, S Bakovic, P Gual
1Institute for Cancer Research and Treatment (IRCC), University of Torino, School of Medicine 10060, Candiolo, Italy.
Oncogene
|June 29, 2000
Summary
Scatter factor receptors MET and RON engage in transphosphorylation, directly activating each other upon ligand binding. This cross-talk is crucial for invasive growth signaling pathways.
Area of Science:
- Cell Biology
- Molecular Oncology
- Signal Transduction
Background:
- Scatter Factors, including HGF (Scatter factor 1) and MSP (Scatter Factor 2), regulate invasive growth.
- These factors bind to tyrosine kinase receptors MET and RON, proto-oncogenes implicated in cancer.
Purpose of the Study:
- To investigate the mechanism of MET and RON receptor activation and their interaction.
- To elucidate the role of transphosphorylation in scatter factor signaling.
Main Methods:
- Utilized kinase-inactive mutant receptors to study MET and RON activation.
- Employed cross-linking experiments to detect cell surface receptor complexes.
- Analyzed tyrosine phosphorylation sites involved in kinase up-regulation and signal transducer docking.
Main Results:
- Ligand-induced activation of MET leads to RON transphosphorylation, and vice versa.
- Transphosphorylation occurs directly between MET and RON receptors, independent of other signal transducers.
- Non-covalent MET-RON complexes form on the cell surface prior to ligand-induced dimerization.
- Kinase-inactive RON exhibits a dominant-negative effect on oncogenic MET mutants.
Conclusions:
- Scatter factor receptors MET and RON exhibit specific cross-talk and cooperate in intracellular signaling.
- Transphosphorylation is a key mechanism for scatter factor-mediated invasive growth.
- Receptor heterodimerization and transphosphorylation are critical for MET and RON signaling pathways.