title: Phosphorylation of the rat Ins(1,4,5)P₃ receptor at T930 within the coupling domain decreases its affinity to Ins(1,4,5)P₃.
abstract: The Ins(1,4,5)P 3 receptor acts as a central hub for Ca ( 2+)  signaling by integrating multiple signaling modalities into Ca ( 2+)  release from intracellular stores downstream of G-protein and tyrosine kinase-coupled receptor stimulation. As such, the Ins(1,4,5)P 3 receptor plays fundamental roles in cellular physiology. The regulation of the Ins(1,4,5)P 3 receptor is complex and involves protein-protein interactions, post-translational modifications, allosteric modulation, and regulation of its sub-cellular distribution. Phosphorylation has been implicated in the sensitization of Ins(1,4,5)P 3-dependent Ca ( 2+)  release observed during oocyte maturation. Here we investigate the role of phosphorylation at T-930, a residue phosphorylated specifically during meiosis. We show that a phosphomimetic mutation at T-930 of the rat Ins(1,4,5)P 3 receptor results in decreased Ins(1,4,5)P 3-dependent Ca ( 2+)  release and lowers the Ins(1,4,5)P 3 binding affinity of the receptor. These data, coupled to the sensitization of Ins(1,4,5)P 3-dependent Ca ( 2+)  release during meiosis, argue that phosphorylation within the coupling domain of the Ins(1,4,5)P 3 receptor acts in a combinatorial fashion to regulate Ins(1,4,5)P 3 receptor function.
authors.affiliation: University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: Shirley
authors.initials: S
authors.lastname: Haun
authors.forename: Lu
authors.initials: L
authors.lastname: Sun
authors.forename: Satanay
authors.initials: S
authors.lastname: Hubrack
authors.forename: David
authors.initials: D
authors.lastname: Yule
authors.forename: Khaled
authors.initials: K
authors.lastname: Machaca
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002645:Chickens; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000235:genetics / Q000378:metabolism*; D008540:Meiosis; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011485:Protein Binding; D051381:Rats; D013912:Threonine / Q000378:metabolism; D014981:Xenopus / Q000378:metabolism
chemical_list: D053496:Inositol 1,4,5-Trisphosphate Receptors; D013912:Threonine; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium