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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
33
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pubmed:dateCreated |
2004-8-9
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pubmed:abstractText |
We show herein that removal of the first 86 amino acids (aa) of the N terminus (designated N) of type VI adenylyl cyclase (ACVI) caused the resultant ACVI mutant (ACVI-DeltaA87) to be more greatly inhibited by a Galpha(i)-coupled receptor or activated Galpha(i) protein. Moreover, in vitro binding of the full-length N and C1a domain (designated C1a), which interacts with Galpha(i), was detected. A truncated N terminus (aa 1-86) also interacted with C1a, suggesting that the C1a-interacting region is located within aa 1-86. Mutation analyses further revealed that N might interact with C1a in the region (aa 434-505) where Galpha(i) is bound. Mutations of two residues (Leu-472 and Val-476) located in this N-binding region of C1a suppressed the interaction between recombinant N and C1a and markedly reduced Galpha(i)-mediated inhibition of ACVI-DeltaA87. Further biochemical analyses of the effect of internal mutations of Leu-472/Val-476 on Galpha(i)-mediated inhibition of wild-type ACVI and ACVI-DeltaA87 suggested that N modulates the Galpha(i)-mediated inhibition of ACVI via binding to C1a when the level of Galpha(i) is low (i.e. around the IC(50) value) and that a more complicated interfering mode results when the level of Galpha(i) is high (i.e. approximately 10- to 20-fold of the IC(50) value). Collectively, data presented herein suggest a novel function of the N terminus of ACVI in Galpha(i)-mediated regulation.
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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/Adenylate Cyclase,
http://linkedlifedata.com/resource/pubmed/chemical/GNAI2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Protein alpha Subunit...,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Protein alpha...,
http://linkedlifedata.com/resource/pubmed/chemical/Gnai2 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Leucine,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Isoforms,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Valine,
http://linkedlifedata.com/resource/pubmed/chemical/adenylyl cyclase 6
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
13
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pubmed:volume |
279
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
34440-8
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15192109-Adenylate Cyclase,
pubmed-meshheading:15192109-Animals,
pubmed-meshheading:15192109-Blotting, Western,
pubmed-meshheading:15192109-CHO Cells,
pubmed-meshheading:15192109-Catalytic Domain,
pubmed-meshheading:15192109-Cell Line,
pubmed-meshheading:15192109-Cell Membrane,
pubmed-meshheading:15192109-Cricetinae,
pubmed-meshheading:15192109-Dose-Response Relationship, Drug,
pubmed-meshheading:15192109-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:15192109-GTP-Binding Protein alpha Subunit, Gi2,
pubmed-meshheading:15192109-GTP-Binding Protein alpha Subunits, Gi-Go,
pubmed-meshheading:15192109-Humans,
pubmed-meshheading:15192109-Inhibitory Concentration 50,
pubmed-meshheading:15192109-Leucine,
pubmed-meshheading:15192109-Models, Biological,
pubmed-meshheading:15192109-Models, Molecular,
pubmed-meshheading:15192109-Mutagenesis, Site-Directed,
pubmed-meshheading:15192109-Mutation,
pubmed-meshheading:15192109-Plasmids,
pubmed-meshheading:15192109-Polymerase Chain Reaction,
pubmed-meshheading:15192109-Protein Binding,
pubmed-meshheading:15192109-Protein Conformation,
pubmed-meshheading:15192109-Protein Isoforms,
pubmed-meshheading:15192109-Protein Structure, Secondary,
pubmed-meshheading:15192109-Protein Structure, Tertiary,
pubmed-meshheading:15192109-Proto-Oncogene Proteins,
pubmed-meshheading:15192109-Rats,
pubmed-meshheading:15192109-Recombinant Proteins,
pubmed-meshheading:15192109-Transfection,
pubmed-meshheading:15192109-Valine
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pubmed:year |
2004
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pubmed:articleTitle |
An important functional role of the N terminus domain of type VI adenylyl cyclase in Galphai-mediated inhibition.
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pubmed:affiliation |
Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan, ROC.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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