Phospholipase C-gamma as a signal-transducing element.
A ubiquitous signaling event in hormonal responses is the phospholipase C (PLC)-catalyzed hydrolysis of phosphatidylinositol 4, 5-bisphosphate to produce the metabolite second messenger molecules inositol 1,4,5-trisphosphate and diacylglycerol. The former provokes a transient increase in intracellular free Ca(2+), while the latter serves as a direct activator of protein kinase C. In tyrosine kinase-dependent signaling pathways this reaction is mediated by the PLC-gamma isozymes. These are direct substrates of many tyrosine kinases in a wide variety of cell types. The mechanism of PLC-gamma activation involves its association with and phosphorylation by receptor and non-receptor tyrosine kinases, as well as interaction with specialized adaptor molecules and, perhaps, other second messenger molecules. However, the biochemistry of PLC-gamma is at a more advanced state than a clear understanding of exactly how this signaling element functions in the generation of a mitogenic response.
Carpenter
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Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee, 37232-0146, USA. Graham.Carpenter@mcmail.vanderbilt.edu
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D004789:Enzyme Activation; D005306:Fertilization / Q000502:physiology; D007527:Isoenzymes / Q000378:metabolism*; D008214:Lymphocytes / Q000276:immunology; D051966:Phospholipase C gamma; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D011946:Receptors, Antigen / Q000378:metabolism; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000378:metabolism*
D007527:Isoenzymes; D011946:Receptors, Antigen; D020794:Receptor Protein-Tyrosine Kinases; D010738:Type C Phospholipases; D051966:Phospholipase C gamma