Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2004-11-24
pubmed:abstractText
Using single cell, real-time imaging, this study compared the impact of members of the B/R4 subfamily of the regulators of G-protein signaling (RGS) (RGS2, -3, and -4) on receptor-mediated inositol 1,4,5-trisphosphate [Ins(1,4,5)P3], diacylglycerol, and Ca2+ signaling. In human embryonic kidney (HEK) 293 cells expressing recombinant Galpha(q/11)-coupled muscarinic M3 receptors, transient coexpression of RGS proteins with fluorescently-tagged biosensors for either Ins(1,4,5)P3 or diacylglycerol demonstrated that RGS2 and 3 inhibited receptor-mediated events. Although gross indices of signaling were unaffected by RGS4, it slowed the rate of increase in Ins(1,4,5)P3 levels. At equivalent levels of expression, myc-tagged RGS proteins showed inhibitory activity on the order RGS3 > or = RGS2 > RGS4. In HEK293 cells, stable expression of myc-tagged RGS2, -3, or -4 at equivalent levels also inhibited phosphoinositide and Ca2+ signaling by endogenously expressed muscarinic M3 receptors in the order RGS3 > or = RGS2 > RGS4. In these cells, RGS2 or -3 reduced receptor-mediated inositol phosphate generation in cell populations and reduced both the magnitude and kinetics (rise-time) of single cell Ca2+ signals. Furthermore, at low levels of receptor activation, oscillatory Ca2+ signals were dampened or abolished, whereas at higher levels, RGS2 and -3 promoted the conversion of more stable Ca2+ elevations into oscillatory signals. Despite little or no effect on responses to maximal receptor activation, RGS4 produced effects on the magnitude, kinetics, and oscillatory behavior of Ca2+ signaling at submaximal levels that were consistent with those of RGS2 and -3.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Calcium, http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Protein alpha..., http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/GTPase-Activating Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Inositol 1,4,5-Trisphosphate, http://linkedlifedata.com/resource/pubmed/chemical/Methacholine Chloride, http://linkedlifedata.com/resource/pubmed/chemical/RGS Proteins, http://linkedlifedata.com/resource/pubmed/chemical/RGS2 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/RGS3 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/RGS4 protein, http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Muscarinic M3, http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Type C Phospholipases
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
66
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1453-64
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15383626-Calcium, pubmed-meshheading:15383626-Cell Line, pubmed-meshheading:15383626-GTP-Binding Protein alpha Subunits, Gq-G11, pubmed-meshheading:15383626-GTP-Binding Proteins, pubmed-meshheading:15383626-GTPase-Activating Proteins, pubmed-meshheading:15383626-Genes, myc, pubmed-meshheading:15383626-Homeostasis, pubmed-meshheading:15383626-Humans, pubmed-meshheading:15383626-Inositol 1,4,5-Trisphosphate, pubmed-meshheading:15383626-Kidney, pubmed-meshheading:15383626-Methacholine Chloride, pubmed-meshheading:15383626-Microscopy, Confocal, pubmed-meshheading:15383626-RGS Proteins, pubmed-meshheading:15383626-Receptor, Muscarinic M3, pubmed-meshheading:15383626-Recombinant Proteins, pubmed-meshheading:15383626-Signal Transduction, pubmed-meshheading:15383626-Transfection, pubmed-meshheading:15383626-Type C Phospholipases
pubmed:year
2004
pubmed:articleTitle
Single-cell imaging of intracellular Ca2+ and phospholipase C activity reveals that RGS 2, 3, and 4 differentially regulate signaling via the Galphaq/11-linked muscarinic M3 receptor.
pubmed:affiliation
Department of Cell Physiology and Pharmacology, University of Leicester, Leicester, United Kingdom.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't