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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
31
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pubmed:dateCreated |
1988-12-2
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pubmed:abstractText |
Numerous plasma membrane-bound receptors are coupled to various effectors via a family of guanine nucleotide regulatory proteins (G proteins). Amino acid sequences of these receptors, deduced from cDNA and genomic clones, indicate the presence of seven transmembrane-spanning domains. Alignment of the available amino acid sequences of these G protein-linked receptors reveals striking homologies in regions predicted to lie near the cytoplasmic surface of the cell membrane. As these areas are likely those which interact with G proteins, we reasoned that systematic introduction of non-native sequence into these highly conserved regions of the human beta 2-adrenergic receptor would allow resolution of loci participating directly in receptor-G protein coupling. Based on this strategy, we constructed 19 mutant receptor species comprising substitutions and deletions of native sequence in the putative cytoplasmic domains of human beta 2-adrenergic receptor. By monitoring ligand binding characteristics and receptor-mediated stimulation of adenylyl cyclase, we have determined that the C-terminal portion of the third cytoplasmic loop and the N-terminal segment of the cytoplasmic tail appear to be critical for productive receptor-coupling to G proteins. In addition, we have implicated two other areas of the receptor that possibly play supportive roles in maintaining proper orientation of the G protein binding site. These comprise the second cytoplasmic loop and a conserved cysteine residue in the cytoplasmic tail.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
5
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pubmed:volume |
263
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
15985-92
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:2846532-Amino Acid Sequence,
pubmed-meshheading:2846532-Animals,
pubmed-meshheading:2846532-Cell Membrane,
pubmed-meshheading:2846532-Cloning, Molecular,
pubmed-meshheading:2846532-Cytoplasm,
pubmed-meshheading:2846532-Female,
pubmed-meshheading:2846532-GTP-Binding Proteins,
pubmed-meshheading:2846532-Humans,
pubmed-meshheading:2846532-Molecular Sequence Data,
pubmed-meshheading:2846532-Mutation,
pubmed-meshheading:2846532-Oocytes,
pubmed-meshheading:2846532-Protein Biosynthesis,
pubmed-meshheading:2846532-Protein Conformation,
pubmed-meshheading:2846532-Receptors, Adrenergic, beta,
pubmed-meshheading:2846532-Xenopus laevis
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pubmed:year |
1988
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pubmed:articleTitle |
Site-directed mutagenesis of the cytoplasmic domains of the human beta 2-adrenergic receptor. Localization of regions involved in G protein-receptor coupling.
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pubmed:affiliation |
Department of Medicine, Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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