Linked Life Data

9525920

Source:http://linkedlifedata.com/resource/pubmed/id/9525920

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
1998-5-7
pubmed:abstractText
When the unicellular eukaryote Dictyostelium discoideum starves, it senses the local density of other starving cells by simultaneously secreting and sensing a glycoprotein called conditioned medium factor (CMF). When the density of starving cells is high, the corresponding high density of CMF permits signal transduction through cAR1, the chemoattractant cAMP receptor. cAR1 activates a heterotrimeric G protein whose alpha-subunit is Galpha2. CMF regulates cAMP signal transduction in part by regulating the lifetime of the cAMP-stimulated Galpha2-GTP configuration. We find here that guanosine 5'-3-O-(thio)triphosphate (GTPgammaS) inhibits the binding of CMF to membranes, suggesting that the putative CMF receptor is coupled to a G protein. Cells lacking Galpha1 (Galpha1 null) do not exhibit GTPgammaS inhibition of CMF binding and do not exhibit CMF regulation of cAMP signal transduction, suggesting that the putative CMF receptor interacts with Galpha1. Work by others has suggested that Galpha1 inhibits phospholipase C (PLC), yet when cells lacking either Galpha1 or PLC were starved at high cell densities (and thus in the presence of CMF), they developed normally and had normal cAMP signal transduction. We find that CMF activates PLC. Galpha1 null cells starved in the absence or presence of CMF behave in a manner similar to control cells starved in the presence of CMF in that they extend pseudopods, have an activated PLC, have a low cAMP-stimulated GTPase, permit cAMP signal transduction, and aggregate. Cells lacking Gbeta have a low PLC activity that cannot be stimulated by CMF. Cells lacking PLC exhibit IP3 levels and cAMP-stimulated GTP hydrolysis rates intermediate to what is observed in wild-type cells starved in the absence or in the presence of an optimal amount of CMF. We hypothesize that CMF binds to its receptor, releasing Gbetagamma from Galpha1. This activates PLC, which causes the Galpha2 GTPase to be inhibited, prolonging the lifetime of the cAMP-activated Galpha2-GTP configuration. This, in turn, allows cAR1-mediated cAMP signal transduction to take place.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
3
pubmed:volume
273
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8161-8
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Cell density sensing mediated by a G protein-coupled receptor activating phospholipase C.
pubmed:affiliation
Howard Hughes Medical Institute, Department of Biochemistry and Cell Biology, MS-140, Rice University, Houston, Texas 77005-1892, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't