マツウラ　トオル   MATSUURA TORU   松浦　徹    所属   関西医科大学  病理学講座    職種   講師
論文種別	原著(症例報告除く)
言語種別	英語
査読の有無	査読あり
表題	G-protein-coupled receptor kinase-interacting proteins inhibit apoptosis by inositol 1,4,5-triphosphate receptor-mediated Ca2+ signal regulation
掲載誌名	正式名：Journal of Biological Chemistry 略　 称：J Biol Chem ISSNコード：00219258
巻・号・頁	284(42),pp.29158-29169
著者・共著者	Songbai Zhang, Chihiro Hisatsune, Toru Matsu-ura, Katsuhiko Mikoshiba
発行年月	2009/10
概要	The inositol 1,4,5-trisphosphate (IP(3)) receptor (IP(3)R) is an intracellular IP(3)-gated calcium (Ca(2+)) release channel and plays important roles in regulation of numerous Ca(2+)-dependent cellular responses. Many intracellular modulators and IP(3)R-binding proteins regulate the IP(3)R channel function. Here we identified G-protein-coupled receptor kinase-interacting proteins (GIT), GIT1 and GIT2, as novel IP(3)R-binding proteins. We found that both GIT1 and GIT2 directly bind to all three subtypes of IP(3)R. The interaction was favored by the cytosolic Ca(2+) concentration and it functionally inhibited IP(3)R activity. Knockdown of GIT induced and accelerated caspase-dependent apoptosis in both unstimulated and staurosporine-treated cells, which was attenuated by wild-type GIT1 overexpression or pharmacological inhibitors of IP(3)R, but not by a mutant form of GIT1 that abrogates the interaction. Thus, we conclude that GIT inhibits apoptosis by modulating the IP(3)R-mediated Ca(2+) signal through a direct interaction with IP(3)R in a cytosolic Ca(2+)-dependent manner.