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Published on: September 20, 2011
Functionally distinct G proteins selectively couple different receptors to PI hydrolysis in the same cell
A Ashkenazi1, E G Peralta, J W Winslow
1Department of Molecular Biology Genentech, Inc., South San Francisco, California 94080.
Cell
|February 10, 1989
Summary
Cells use multiple G proteins (Gp) to activate phospholipase C, coupling selectively to different receptors. This G protein diversity fine-tunes cellular responses by modulating phosphoinositide hydrolysis.
Area of Science:
- Cellular signaling pathways
- G protein-coupled receptors
- Signal transduction mechanisms
Background:
- The known functions of G proteins do not match the number identified through molecular cloning.
- Understanding the specific roles of different G proteins in cellular processes is crucial.
Purpose of the Study:
- To investigate if multiple G proteins can mediate the same function, such as phospholipase C activation, by coupling to distinct receptors.
- To characterize these G proteins (Gp) and their selective receptor coupling.
- To determine how Gp pathways influence cellular responses.
Main Methods:
- Utilizing molecular cloning to introduce receptors into cells.
- Assessing phospholipase C activation and phosphoinositide (PI) hydrolysis.
- Employing pertussis toxin sensitivity to differentiate G proteins.
- Analyzing additivity relationships of PI hydrolysis responses to confirm receptor-pathway assignments.
Main Results:
- Cells possess multiple G proteins (Gp) that activate phospholipase C but couple selectively to different receptors (endogenous or transfected).
- Gp pathways can be distinguished by their sensitivity to pertussis toxin.
- Additivity of PI hydrolysis responses confirmed specific receptor-Gp pathway assignments.
- Different Gp pathways activate significantly different amounts of PI hydrolysis, indicating varying coupling efficiencies to phospholipase C.
Conclusions:
- Distinct Gp pathways exist within a single cell to selectively link different receptors to phospholipase C activation.
- These Gp pathways contribute to the specificity of cellular responses to various extracellular signals by modulating the magnitude of PI hydrolysis.
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