Abstract
RACK1 is not a G protein but closely resembles the heterotrimeric Gbeta-subunit. RACK1 serves as a scaffold, linking protein kinase C to its substrates. We demonstrate that RACK1 physiologically binds inositol 1,4,5-trisphosphate receptors and regulates Ca2+ release by enhancing inositol 1,4,5-trisphosphate receptor binding affinity for inositol 1,4,5-trisphosphate. Overexpression of RACK1 or depletion of RACK1 by interference RNA markedly augments or diminishes Ca2+ release, respectively, without affecting Ca2+ entry. These findings establish RACK1 as a physiologic mediator of agonist-induced Ca2+ release.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Substitution
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Animals
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Calcium / physiology*
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Calcium Channels / chemistry
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Calcium Channels / metabolism*
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Calcium Signaling
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Cell Line
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GTP-Binding Proteins
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Humans
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Inositol 1,4,5-Trisphosphate Receptors
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Kidney
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Kinetics
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Mutagenesis, Site-Directed
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Neoplasm Proteins / chemistry
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Neoplasm Proteins / deficiency
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Neoplasm Proteins / metabolism*
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PC12 Cells
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Protein Binding
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RNA, Small Interfering / genetics
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Rats
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Receptors for Activated C Kinase
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Receptors, Cell Surface
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Receptors, Cytoplasmic and Nuclear / chemistry
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Receptors, Cytoplasmic and Nuclear / metabolism*
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Recombinant Proteins / chemistry
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Recombinant Proteins / metabolism
Substances
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Calcium Channels
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ITPR1 protein, human
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Inositol 1,4,5-Trisphosphate Receptors
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Neoplasm Proteins
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RACK1 protein, human
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RNA, Small Interfering
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Receptors for Activated C Kinase
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Receptors, Cell Surface
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Receptors, Cytoplasmic and Nuclear
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Recombinant Proteins
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GTP-Binding Proteins
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Calcium