RACK1 binds to inositol 1,4,5-trisphosphate receptors and mediates Ca2+ release.
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.
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Randen L
RL
Patterson
Damian B
DB
van Rossum
Roxanne K
RK
Barrow
Solomon H
SH
Snyder
D019943:Amino Acid Substitution; D000818:Animals; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000737:chemistry / Q000378:metabolism*; D020013:Calcium Signaling; D002460:Cell Line; D019204:GTP-Binding Proteins; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007668:Kidney; D007700:Kinetics; D016297:Mutagenesis, Site-Directed; D009363:Neoplasm Proteins / Q000737:chemistry / Q000172:deficiency / Q000378:metabolism*; D016716:PC12 Cells; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism
D015220:Calcium Channels; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D009363:Neoplasm Proteins; C419368:RACK1 protein, human; D034741:RNA, Small Interfering; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D011994:Recombinant Proteins; D019204:GTP-Binding Proteins; D002118:Calcium