Cargando…

Signal transduction mechanisms involved in hormonal Ca2+ fluxes.

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 betw...

Descripción completa

Detalles Bibliográficos
Autores principales: Williamson, J R, Monck, J R
Formato: Texto
Lenguaje:English
Publicado: 1990
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1567633/
https://www.ncbi.nlm.nih.gov/pubmed/2190806
_version_ 1782129868842991616
author Williamson, J R
Monck, J R
author_facet Williamson, J R
Monck, J R
author_sort Williamson, J R
collection PubMed
description 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.
format Text
id pubmed-1567633
institution National Center for Biotechnology Information
language English
publishDate 1990
record_format MEDLINE/PubMed
spelling pubmed-15676332006-09-18 Signal transduction mechanisms involved in hormonal Ca2+ fluxes. Williamson, J R Monck, J R Environ Health Perspect Research Article 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. 1990-03 /pmc/articles/PMC1567633/ /pubmed/2190806 Text en
spellingShingle Research Article
Williamson, J R
Monck, J R
Signal transduction mechanisms involved in hormonal Ca2+ fluxes.
title Signal transduction mechanisms involved in hormonal Ca2+ fluxes.
title_full Signal transduction mechanisms involved in hormonal Ca2+ fluxes.
title_fullStr Signal transduction mechanisms involved in hormonal Ca2+ fluxes.
title_full_unstemmed Signal transduction mechanisms involved in hormonal Ca2+ fluxes.
title_short Signal transduction mechanisms involved in hormonal Ca2+ fluxes.
title_sort signal transduction mechanisms involved in hormonal ca2+ fluxes.
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1567633/
https://www.ncbi.nlm.nih.gov/pubmed/2190806
work_keys_str_mv AT williamsonjr signaltransductionmechanismsinvolvedinhormonalca2fluxes
AT monckjr signaltransductionmechanismsinvolvedinhormonalca2fluxes