The phospholipase C isozymes and their regulation
Aurelie Gresset1, John Sondek, T Kendall Harden
1Department of Pharmacology, University of North Carolina School of Medicine, 27599, Chapel Hill, NC, USA.
Sub-Cellular Biochemistry
|March 10, 2012
Summary
Phospholipase C (PLC) enzymes regulate vital cell signaling pathways. Their activation involves removing an autoinhibitory mechanism in the catalytic core, crucial for cellular responses.
Area of Science:
- Biochemistry
- Cell Biology
- Molecular Signaling
Background:
- Extracellular signals activate phospholipase C (PLC) to mediate physiological effects.
- PLC triggers inositol lipid signaling pathways, producing second messengers like inositol(1,4,5)P(3) and diacylglycerol.
- Mammalian cells express 13 PLC isozymes, each with a catalytic core and regulatory mechanisms.
Purpose of the Study:
- To elucidate the regulatory mechanisms of phospholipase C (PLC) isozymes.
- To understand how different PLC subclasses are activated by various signaling molecules.
- To investigate the structural basis of PLC activation.
Main Methods:
- Analysis of high-resolution three-dimensional structures of PLC enzymes.
- Biochemical studies to probe enzyme activity and regulation.
- Investigating the role of the X/Y linker region in PLC autoinhibition.
Main Results:
- PLC isozymes share a catalytic core, with variations conferring distinct regulatory modes.
- PLC-b is activated by G protein subunits, PLC-g by tyrosine kinases, and PLC-e/some PLC-b/g by small GTPases.
- The X/Y linker region of the catalytic core mediates autoinhibition, which is relieved upon activation.
Conclusions:
- Activation of PLC isozymes involves the removal of autoinhibition mediated by the X/Y linker region.
- Diverse signaling pathways converge on PLC activation through various upstream regulators.
- Understanding PLC regulation is key to comprehending fundamental cellular processes.
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