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G-proteins, the inositol lipid signalling pathway, and secretion
1Department of Experimental Pathology, School of Medicine, University College London, U.K.
Summary
G-proteins regulate cell signaling pathways. This review highlights a novel G-protein family (GP) activating polyphosphoinositide phosphodiesterase (PPI-PDE) and another G-protein (GE) involved in secretion.
Area of Science:
- Cellular signaling pathways
- G-protein coupled receptors
- Second messenger systems
Background:
- Guanine nucleotide regulatory proteins (G-proteins) link receptors to effectors.
- Cyclic AMP (cAMP) formation is mediated by G-protein GS.
- Calcium (Ca2+)-mobilizing receptors activate phosphatidylinositol bisphosphate (PtdIns(4,5)P2) hydrolysis, generating Ins(1,4,5)P3 and diacylglycerol.
Purpose of the Study:
- To review evidence for a three-component signaling system: receptor, G-protein, and effector.
- To identify novel G-proteins involved in cellular signaling and secretion.
Main Methods:
- Review of existing scientific literature and evidence.
- Analysis of cellular responses to G-protein activation.
- Pertussis toxin sensitivity assays to characterize G-proteins.
Main Results:
- A novel G-protein, GP, activates polyphosphoinositide phosphodiesterase (PPI-PDE) and exhibits variable pertussis toxin sensitivity.
- GP represents a family of proteins activating PPI-PDE.
- Another G-protein, GE, is implicated in cellular secretion, activated by guanine nucleotide analogues independently of PPI-PDE.
Conclusions:
- Cellular signaling involves a complex interplay of receptors, G-proteins, and effectors.
- The G-protein GP is a diverse family crucial for PPI-PDE activation.
- The G-protein GE plays a distinct role in regulating secretory processes.