Structure, function, and control of phosphoinositide-specific phospholipase C.
Phosphoinositide-specific phospholipase C (PLC) subtypes beta, gamma, and delta comprise a related group of multidomain phosphodiesterases that cleave the polar head groups from inositol lipids. Activated by all classes of cell surface receptor, these enzymes generate the ubiquitous second messengers inositol 1,4, 5-trisphosphate and diacylglycerol. The last 5 years have seen remarkable advances in our understanding of the molecular and biological facets of PLCs. New insights into their multidomain arrangement and catalytic mechanism have been gained from crystallographic studies of PLC-delta(1), while new modes of controlling PLC activity have been uncovered in cellular studies. Most notable is the realization that PLC-beta, -gamma, and -delta isoforms act in concert, each contributing to a specific aspect of the cellular response. Clues to their true biological roles were also obtained. Long assumed to function broadly in calcium-regulated processes, genetic studies in yeast, slime molds, plants, flies, and mammals point to specific and conditional roles for each PLC isoform in cell signaling and development. In this review we consider each subtype of PLC in organisms ranging from yeast to mammals and discuss their molecular regulation and biological function.
Rebecchi
M J
MJ
Departments of Anesthesiology and Physiology and Biophysics, School of Medicine, State University of New York, Stony Brook, New York 11794, USA. Rebecchi@epo.sunysb.edu
Pentyala
S N
SN
D000818:Animals; D030801:Animals, Genetically Modified; D001665:Binding Sites; D002384:Catalysis; D002455:Cell Division; D004023:Dictyostelium; D020832:EF Hand Motifs / Q000502:physiology; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D009928:Organ Specificity; D010716:Phosphatidylinositols / Q000378:metabolism*; D010766:Phosphorylation; D010944:Plants; D017434:Protein Structure, Tertiary / Q000502:physiology; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D013379:Substrate Specificity / Q000502:physiology; D010738:Type C Phospholipases / Q000235:genetics / Q000378:metabolism*; D015003:Yeasts
D007527:Isoenzymes; D010716:Phosphatidylinositols; D011956:Receptors, Cell Surface; D020794:Receptor Protein-Tyrosine Kinases; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins