| Phosducin-like protein regulates G-protein betagamma folding by interaction with tailless complex polypeptide-1alpha: dephosphorylation or splicing of PhLP turns the switch toward regulation of Gbetagamma folding. | |
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MedLine Citation:
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PMID: 15745879 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Phosducin-like protein (PhLP) exists in two splice variants PhLP(LONG) (PhLP(L)) and PhLP(SHORT) (PhLP(S)). Whereas PhLP(L) directly inhibits Gbetagamma-stimulated signaling, the G betagamma-inhibitory mechanism of PhLP(S) is not understood. We report here that inhibition of Gbetagamma signaling in intact HEK cells by PhLP(S) was independent of direct Gbetagamma binding; however, PhLP(S) caused down-regulation of Gbeta and Ggamma proteins. The down-regulation was partially suppressed by lactacystine, indicating the involvement of proteasomal degradation. N-terminal fusion of Gbeta or Ggamma with a dye-labeling protein resulted in their stabilization against down-regulation by PhLP(S) but did not lead to a functional rescue. Moreover, in the presence of PhLP(S), stabilized Ggamma subunits did not coprecipitate with stabilized Gbeta subunits, suggesting that PhLP(S) might interfere with Gbetagamma folding. PhLP(S) and several truncated mutants of PhLP(S) interacted with the subunit tailless complex polypeptide-1alpha (TCP-1alpha) of the CCT chaperonin complex, which is involved in protein folding. Knock-down of TCP-1alpha in HEK cells by small interfering RNA also led to down-regulation of Gbetagamma. We therefore conclude that the strong inhibitory action of PhLP(S) on Gbetagamma signaling is the result of a previously unrecognized mechanism of Gbetagamma-regulation, inhibition of Gbetagamma-folding by interference with TCP-1alpha. |
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Authors:
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Jan Humrich; Christina Bermel; Moritz Bünemann; Linda Härmark; Robert Frost; Ursula Quitterer; Martin J Lohse |
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Publication Detail:
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Type: In Vitro; Journal Article Date: 2005-03-02 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 280 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 2005 May |
Date Detail:
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Created Date: 2005-05-17 Completed Date: 2005-07-08 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 20042-50 Citation Subset: IM |
Affiliation:
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Institute of Pharmacology and Toxicology, University of Wuerzburg, Germany. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Base Sequence Carrier Proteins / chemistry, genetics, metabolism* Casein Kinase II / genetics, metabolism Cell Line Chaperonin Containing TCP-1 Chaperonins / chemistry*, genetics, metabolism* DNA, Complementary / genetics GTP-Binding Protein beta Subunits / chemistry*, genetics, metabolism* GTP-Binding Protein gamma Subunits / chemistry*, genetics, metabolism* Humans Models, Biological Molecular Sequence Data Multiprotein Complexes Nerve Tissue Proteins / chemistry, genetics, metabolism* Protein Binding Protein Folding Protein Isoforms / chemistry, genetics, metabolism Protein Subunits RNA Interference RNA, Small Interfering / genetics Recombinant Proteins / chemistry, genetics, metabolism Sequence Homology, Amino Acid |
| Chemical | |
Reg. No./Substance:
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0/Carrier Proteins; 0/DNA, Complementary; 0/G-protein Beta gamma; 0/GTP-Binding Protein beta Subunits; 0/GTP-Binding Protein gamma Subunits; 0/Multiprotein Complexes; 0/Nerve Tissue Proteins; 0/PDCL protein, human; 0/Protein Isoforms; 0/Protein Subunits; 0/RNA, Small Interfering; 0/Recombinant Proteins; EC 2.7.11.1/Casein Kinase II; EC 3.6.1.-/Chaperonin Containing TCP-1; EC 3.6.1.-/Chaperonins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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