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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
27
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pubmed:dateCreated |
2009-6-29
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pubmed:abstractText |
Regulator of G-protein signaling (RGS) proteins are a family of molecules that control the duration of G protein signaling. A variety of RGS proteins have been reported to modulate opioid receptor signaling. Here we show that RGS4 is abundantly expressed in human neuroblastoma SH-SY5Y cells that endogenously express mu- and delta-opioid receptors and test the hypothesis that the activity of opioids in these cells is modulated by RGS4. Endogenous RGS4 protein was reduced by approximately 90% in SH-SY5Y cells stably expressing short hairpin RNA specifically targeted to RGS4. In these cells, the potency and maximal effect of delta-opioid receptor agonist (SNC80)-mediated inhibition of forskolin-stimulated cAMP accumulation was increased compared with control cells. This effect was reversed by transient transfection of a stable RGS4 mutant (HA-RGS4C2S). Furthermore, MAPK activation by SNC80 was increased in cells with knockdown of RGS4. In contrast, there was no change in the mu-opioid (morphine) response at adenylyl cyclase or MAPK. FLAG-tagged opioid receptors and HA-RGS4C2S were transiently expressed in HEK293T cells, and co-immunoprecipitation experiments showed that the delta-opioid receptor but not the mu-opioid receptor could be precipitated together with the stable RGS4. Using chimeras of the delta- and mu-opioid receptors, the C-tail and third intracellular domain of the delta-opioid receptor were suggested to be the sites of interaction with RGS4. The findings demonstrate a role for endogenous RGS4 protein in modulating delta-opioid receptor signaling in SH-SY5Y cells and provide evidence for a receptor-specific effect of RGS4.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19416973-10517644,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19416973-10542401,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19416973-11065178,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19416973-11076532,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19416973-11152677,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19416973-11356902,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19416973-11771424,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19416973-11786497,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19416973-12006602,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19416973-12082117,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19416973-12120503,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19416973-12223533,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19416973-12524446,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19416973-12604710,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19416973-12815156,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19416973-12885912,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19416973-14595021,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19416973-14604980,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19416973-14997173,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19416973-15313565,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19416973-15313570,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19416973-15734717,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19416973-15781518,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19416973-15793568,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19416973-15827571,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19416973-16120478,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19416973-16539683,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19416973-16647283,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19416973-1697894,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19416973-17220356,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19416973-17433292,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19416973-17725581,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19416973-17880927,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19416973-17980352,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19416973-1847209,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19416973-18703511,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19416973-2552439,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19416973-2834542,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19416973-3040240,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19416973-7515530,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19416973-7535487,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19416973-8789387,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19416973-8981566,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19416973-9003025,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19416973-9012799,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19416973-9302102,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19416973-9400003,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19416973-9856989,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19416973-9920901
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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/4-(alpha-(4-allyl-2,5-dimethyl-1-pip...,
http://linkedlifedata.com/resource/pubmed/chemical/Analgesics, Opioid,
http://linkedlifedata.com/resource/pubmed/chemical/Benzamides,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Enkephalin, Ala(2)-MePhe(4)-Gly(5)-,
http://linkedlifedata.com/resource/pubmed/chemical/Forskolin,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Morphine,
http://linkedlifedata.com/resource/pubmed/chemical/Piperazines,
http://linkedlifedata.com/resource/pubmed/chemical/RGS Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RGS4 protein,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Opioid, delta,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Opioid, mu,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1083-351X
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
3
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pubmed:volume |
284
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
18357-67
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pubmed:dateRevised |
2010-9-27
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pubmed:meshHeading |
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