Abstract
Recently, GBR1, a seven-transmembrane domain protein with high affinity for gamma-aminobutyric acid (GABA)B receptor antagonists, was identified. Here, a GBR1-related protein, GBR2, was shown to be coexpressed with GBR1 in many brain regions and to interact with it through a short domain in the carboxyl-terminal cytoplasmic tail. Heterologously expressed GBR2 mediated inhibition of adenylyl cyclase; however, inwardly rectifying potassium channels were activated by GABAB receptor agonists only upon coexpression with GBR1 and GBR2. Thus, the interaction of these receptors appears to be crucial for important physiological effects of GABA and provides a mechanism in receptor signaling pathways that involve a heterotrimeric GTP-binding protein.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenylyl Cyclase Inhibitors
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Amino Acid Sequence
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Animals
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Brain / metabolism*
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Cell Line
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Cyclic AMP / metabolism
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Dimerization
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G Protein-Coupled Inwardly-Rectifying Potassium Channels
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GABA-B Receptor Agonists
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Humans
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In Situ Hybridization
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Molecular Sequence Data
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Neurons / metabolism
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Potassium / metabolism
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Potassium Channels / metabolism
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Potassium Channels, Inwardly Rectifying*
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Rats
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Receptors, GABA / chemistry*
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Receptors, GABA / metabolism*
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Receptors, GABA-B / chemistry*
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Receptors, GABA-B / metabolism*
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / metabolism
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Sequence Alignment
Substances
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Adenylyl Cyclase Inhibitors
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G Protein-Coupled Inwardly-Rectifying Potassium Channels
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GABA-B Receptor Agonists
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GABBR2 protein, human
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Gabbr2 protein, rat
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Potassium Channels
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Potassium Channels, Inwardly Rectifying
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RNA, Messenger
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Receptors, GABA
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Receptors, GABA-B
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Recombinant Fusion Proteins
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Cyclic AMP
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Potassium