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 |
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Authors: | Shirley Haun Lu Sun Satanay Hubrack David Yule Khaled Machaca |
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Institution: | 1.University of Arkansas for Medical Sciences; Little Rock, AR USA;2.Department of Physiology and Biophysics; Weill Cornell Medical College in Qatar; Doha, Qatar;3.University of Rochester Medical Center; Rochester, NY USA |
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Abstract: | The Ins(1,4,5)P3 receptor acts as a central hub for Ca2+ signaling by integrating multiple signaling modalities into Ca2+ release from intracellular stores downstream of G-protein and tyrosine kinase-coupled receptor stimulation. As such, the Ins(1,4,5)P3 receptor plays fundamental roles in cellular physiology. The regulation of the Ins(1,4,5)P3 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)P3-dependent Ca2+ 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)P3 receptor results in decreased Ins(1,4,5)P3-dependent Ca2+ release and lowers the Ins(1,4,5)P3 binding affinity of the receptor. These data, coupled to the sensitization of Ins(1,4,5)P3-dependent Ca2+ release during meiosis, argue that phosphorylation within the coupling domain of the Ins(1,4,5)P3 receptor acts in a combinatorial fashion to regulate Ins(1,4,5)P3 receptor function. |
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Keywords: | Ca2+ signaling IP3 receptor phosphorylation affinity phosphomimetic |
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