G protein-dependent regulation of phospholipase C by cell surface receptors.
Physiologic responses mediated by calcium-mobilizing receptors are initiated by the phospholipase C-catalyzed generation from phosphatidyl inositol (4,5)-bisphosphate of two intracellular second messengers: inositol (1,4,5)-trisphosphate, which induces the release of calcium from intracellular stores, and diacylglycerol, which stimulates protein kinase C activity. Recent studies illustrating guanine nucleotide dependence for hormonal stimulation of membrane phospholipase C suggest involvement of a guanine nucleotide regulatory protein (G protein) in phosphoinositide/Ca2+ signaling. Kinetic analysis indicates that the receptor-stimulated phospholipase C catalytic cycle expresses properties similar to those described in detail for receptor and G protein-regulated adenylate cyclase. However, the identity of the phospholipase C-associated G protein remains to be established, and available data suggest that different G proteins (at least two) may be involved in a tissue- and/or receptor-specific manner. The identity of the phospholipase C involved in the action of calcium-mobilizing hormones also has not been established. Multiple forms of membrane-associated and cytosolic phospholipase C enzymes have been described during the last few years, which increases the apparent complexity of the system. The identification and purification of the G protein(s) and the phospholipase C enzyme(s) of this important signaling system followed by unambiguous reconstitution of their physiologic activities represent major challenges in this field for the coming years.
Harden
T K
TK
Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill.
D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000502:physiology*; D006133:Growth Substances / Q000502:physiology; D006150:Guanine Nucleotides / Q000502:physiology; D006801:Humans; D011956:Receptors, Cell Surface / Q000502:physiology*; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000302:isolation & purification / Q000378:metabolism*
D006133:Growth Substances; D006150:Guanine Nucleotides; D011956:Receptors, Cell Surface; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins