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Binding of GAP to activated PDGF receptors
A Kazlauskas1, C Ellis, T Pawson
1Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
Science (New York, N.Y.)
|March 30, 1990
Summary
Platelet-derived growth factor (PDGF) signaling involves the Ras GTPase activator protein (GAP). PDGF binding to its receptor recruits GAP, requiring receptor kinase activity and specific tyrosine phosphorylation sites for maximal association.
Area of Science:
- Cellular signaling pathways
- Molecular biology
- Oncogene research
Background:
- Ras proto-oncogene products are key intracellular signal transducers.
- Ras GTPase activator protein (GAP) mediates signals from Ras.
- Platelet-derived growth factor (PDGF) receptors initiate signaling cascades upon ligand binding.
Purpose of the Study:
- To investigate the interaction between PDGF receptors and GAP.
- To elucidate the molecular requirements for GAP association with the PDGF receptor.
Main Methods:
- Utilized dog epithelial cells engineered to express human PDGF receptors.
- Studied the effect of PDGF binding on GAP complex formation.
- Employed mutant PDGF receptors to identify critical domains and activities for receptor-GAP association.
Main Results:
- PDGF binding induced complex formation between GAP and the PDGF receptor in approximately 10% of total GAP molecules.
- Maximum association of GAP with the receptor necessitated active receptor kinase function.
- Specific phosphorylatable tyrosine residues at autophosphorylation sites were essential for robust GAP complexation.
Conclusions:
- The interaction between PDGF receptors and GAP is a critical step in PDGF-mediated intracellular signaling.
- Receptor kinase activity and specific tyrosine phosphorylation sites are indispensable for efficient recruitment of GAP.
- This interaction highlights the intricate regulation of Ras signaling pathways by growth factor receptors.
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