摘要：This article reviews literature up to mid-1988 covering recent developments pertaining to agonist-induced Ca2+ signaling in various cell types. A large amount of experimental evidence supports a mechanism involving specific guanine nucleotide-binding proteins (G-proteins) as transducing factors between occupancy of a wide variety of receptors by many different agonists and activation of polyphosphoinositide specific phospholipase C enzymes. Although many different G-proteins and phospholipase C enzymes have been purified and cloned, successful reconstitution of the components has not been achieved. Hence, many questions concerning the specificity of coupling between particular receptors to a particular G-protein and phospholipase C subtype remain unresolved. Phospholipase C subtypes isolated from the membrane and soluble fractions of the cell are directly activated by Ca2+ and, preferentially, hydrolyse phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol 4-phosphate (PIP). The role of the G-protein is to stimulate inositol lipid breakdown at free Ca2+ concentrations (0.1-0.2 microM) typical of unstimulated cells. Overwhelming evidence supports the concept that Ins 1,4,5-P3, the product of PIP2 hydrolysis, is responsible for the initial agonist-induced Ca2+ transient by mobilization of Ca2+ from a specialized intracellular store. An Ins 1,4,5-P3 receptor has been purified that may correspond to the postulated Ins 1,4,5-P3 gated Ca2+ channel. Despite a growing understanding of the complexities of the metabolism of Ins 1,4,5-P3 and a successful purification of many enzymes involved, including the ATP-dependent 3-kinase that converts Ins 1,4,5-P3 to Ins 1,3,4,5-P4, the role of Ins 1,3,4,5-P4 as a putative second messenger remains enigmatic. Multiple forms of protein kinase C have been described and the role is well established for a 1,2-diacylglycerol, the second product of PIP2 hydrolysis, as its physiological activator. Although protein kinase C has been shown to phosphorylate and modulate the activity of several proteins involved in the Ca2+ signaling pathway and Ca2+ transport, the physiological significance of the protein kinase C in agonist-stimulated cell function requires further elucidation. The extension of measurements of hormone-induced Ca2+ changes to single cells has shown that the occurrence of Ca2+ oscillations is a common phenomena. Elucidation of the biochemical mechanisms causing this oscillatory response and its physiological significance represents an important challenge for future studies. Full text Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (3.6M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References . 121 122 123 124 125 126 127 128 129 130 131 132 133 134 135 136
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