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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
16
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pubmed:dateCreated |
2004-4-21
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pubmed:abstractText |
TRPM7 is a ubiquitously expressed and constitutively active divalent cation-selective ion channel, whose basal activity is regulated by intracellular levels of Mg(2+) and Mg.ATP. We have investigated receptor-mediated mechanisms that may actively regulate TRPM7 activity. We here report that TRPM7 currents are suppressed by intracellular GTPgammaS, suggesting the involvement of heterotrimeric G proteins. TRPM7 currents are also inhibited by stimulating endogenous muscarinic receptors, which is mediated by G(i) because the inhibitory effect is blunted by pertussis toxin. Conversely, stimulation of endogenous G(s)-coupled beta-adrenergic receptors potentiates TRPM7 currents, whereas G(q)-coupled thrombin receptors have little effect. Consistent with the involvement of G(s)/G(i) in controlling adenylyl cyclase activity, elevations of intracellular cAMP levels enhance TRPM7 activity and prevent receptor-mediated modulation of TRPM7 activity by muscarinic and adrenergic agonists. This cAMP-dependent effect requires the functional integrity of both protein kinase A (PKA) and the endogenous kinase domain of TRPM7 because cAMP-mediated effects are abolished when treating cells with the PKA inhibitors H89 or KT5720 as well as in cells expressing phosphotransferase-deficient TRPM7 constructs. These mutant channels are also much less susceptible to GTPgammaS-mediated inhibition, suggesting that the main regulatory effect occurs through G(i)- and G(s)-mediated changes in cAMP. Taken together, our results demonstrate that TRPM7 activity is up- and down-regulated through its endogenous kinase in a cAMP- and PKA-dependent manner.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/15069188-10717675,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15069188-11161216,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15069188-11274183,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15069188-11385574,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15069188-11389472,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15069188-11389851,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15069188-11864597,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15069188-11882677,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15069188-11893331,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15069188-11931992,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15069188-11941371,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15069188-12039967,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15069188-12508053,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15069188-12887921,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15069188-2156866,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15069188-3028414,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15069188-8888308,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15069188-9647869
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ion Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Pertussis Toxin,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface,
http://linkedlifedata.com/resource/pubmed/chemical/TRPM Cation Channels,
http://linkedlifedata.com/resource/pubmed/chemical/TRPM7 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Type C Phospholipases
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0027-8424
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
20
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pubmed:volume |
101
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6009-14
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15069188-Calcium,
pubmed-meshheading:15069188-Cell Line,
pubmed-meshheading:15069188-Cyclic AMP,
pubmed-meshheading:15069188-GTP-Binding Proteins,
pubmed-meshheading:15069188-Humans,
pubmed-meshheading:15069188-Ion Channels,
pubmed-meshheading:15069188-Membrane Proteins,
pubmed-meshheading:15069188-Patch-Clamp Techniques,
pubmed-meshheading:15069188-Pertussis Toxin,
pubmed-meshheading:15069188-Protein Kinases,
pubmed-meshheading:15069188-Receptors, Cell Surface,
pubmed-meshheading:15069188-TRPM Cation Channels,
pubmed-meshheading:15069188-Type C Phospholipases
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pubmed:year |
2004
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pubmed:articleTitle |
Receptor-mediated regulation of the TRPM7 channel through its endogenous protein kinase domain.
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pubmed:affiliation |
Laboratory of Cell and Molecular Signaling, Center for Biomedical Research, The Queen's Medical Center and John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96813, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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