Abstract
This review focuses on the coupling specificity of the Galpha and Gbetagamma subunits of pertussis toxin (PTX)-sensitive G(i/o) proteins that mediate diverse signaling pathways, including regulation of ion channels and other effectors. Several lines of evidence indicate that specific combinations of G protein alpha, beta and gamma subunits are required for different receptors or receptor-effector networks, and that a higher degree of specificity for Galpha and Gbetagamma is observed in intact systems than reported in vitro. The structural determinants of receptor-G protein specificity remain incompletely understood, and involve receptor-G protein interaction domains, and perhaps other scaffolding processes. By identifying G protein specificity for individual receptor signaling pathways, ligands targeted to disrupt individual pathways of a given receptor could be developed.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Adenylyl Cyclases / metabolism
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Amino Acid Sequence
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Animals
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Calcium Channels / metabolism
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GTP-Binding Protein alpha Subunits, Gi-Go / chemistry
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GTP-Binding Protein alpha Subunits, Gi-Go / physiology*
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GTP-Binding Protein beta Subunits*
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GTP-Binding Protein gamma Subunits*
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Heterotrimeric GTP-Binding Proteins / chemistry
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Heterotrimeric GTP-Binding Proteins / metabolism
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Heterotrimeric GTP-Binding Proteins / physiology*
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Humans
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Macromolecular Substances
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Models, Biological
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Potassium Channels / metabolism
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Receptors, Cell Surface / metabolism
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Sequence Alignment
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Signal Transduction*
Substances
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Calcium Channels
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G-protein Beta gamma
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GTP-Binding Protein beta Subunits
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GTP-Binding Protein gamma Subunits
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Macromolecular Substances
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Potassium Channels
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Receptors, Cell Surface
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GTP-Binding Protein alpha Subunits, Gi-Go
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Heterotrimeric GTP-Binding Proteins
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Adenylyl Cyclases