Regulation of phosphoinositide phospholipases by hormones, neurotransmitters, and other agonists linked to G proteins

• Published in: Annual review of pharmacology and toxicology 1996-01, Vol.36 (1), p.481-509
• Main Author: Exton, J H
• Format: Article
• Language: English
• Subjects: Animals; Calcium - metabolism; Diglycerides - metabolism; Diglycerides - pharmacology; Enzyme Activation - drug effects; Growth Substances - metabolism; GTP-Binding Proteins - metabolism; Hormones - metabolism; Inositol 1,4,5-Trisphosphate - metabolism; Isoenzymes - metabolism; Neurotransmitter Agents - metabolism; Phosphatidylinositol Diacylglycerol-Lyase; Phosphoric Diester Hydrolases - chemistry; Phosphoric Diester Hydrolases - metabolism; Phosphotransferases (Alcohol Group Acceptor) - metabolism; Type C Phospholipases - metabolism
• ISSN: 0362-1642; 1545-4304
• DOI: 10.1146/annurev.pa.36.040196.002405

The actions of many hormones, neurotransmitters, and growth factors are mediated by the hydrolysis of phosphatidylinositol 4,5-bisphosphate catalyzed by specific isozymes of phospholipase C. This hydrolysis releases inositol 1,4,5-trisphosphate, which mobilizes Ca2+ ions from components of the endoplasmic reticulum, and 1,2-diacylglycerol, which activates isozymes of protein kinase C. The hormones and neurotransmitters activate beta-isozymes of phospholipase C through receptors that have seven transmembrane segments and couple to G proteins of the Gq and Gi/o families. Activation of phospholipase C by the Gq family involves their alpha-subunits, whereas activation by the Gi/o family involves their beta gamma-subunits. The growth factors activate gamma-isozymes of phospholipase C through receptors that become autophosphorylated due to their stimulated tyrosine kinase activity and provide binding sites for the Src homology domains of the isozymes. The molecular mechanisms by which agonists activate phopholipase isozymes are described in detail.