StudyofintracellularlocalizationofIP3-receptortype2

IP3R-I(IP3R-I)被PKA磷酸化，这导致卡巴胆碱(CCH)诱导IP3R-I钙释放的增强。在IRAG和PKG Iβ存在下，IP3R-I与这些分子形成复合体，从而导致PKA的磷酸化和CCH诱导的钙释放的增强。IP3RⅡ(IP3R-II)也能与IRAG和PKG Iβ形成复合体。然而，PKA对IP3R-II的磷酸化和卡巴胆碱(CCH)诱导的IP3R-II钙释放的增强作用不受形成络合物的抑制。在本研究中，我们确定了与IRAG相互作用所需的IP3R分子区域。在IP3R-I中，该区域非常接近磷酸化位点，而在IP3R-II中，它远离磷酸化位点。这一结果表明，IP3R-I与IRAG在空间上的相互作用不允许PKA进入磷酸化位点。

IP3R type I (IP3R-I) was phosphorylated by PKA and this causesthe potentiation of carbachol (CCh)-induced Ca-release from IP3R-I. In the presence ofIRAG and PKG Iβ, IP3R-I forms a complex with these molecules and this causes theloss of both the phosphorylation by PKA and the potentiation of CCh-inducedCa-release. IP3R type II (IP3R-II) also be able to form a complex with IRAG and PKG Iβ. However, the phosphorylation of IP3R-II by PKA and the potentiation of carbachol(CCh)-induced Ca-release from IP3R-II were not inhibited by forming a complex. Inthis study, we identified the regions of IP3R molecules, which were required forinteraction with IRAG. In the IP3R-I, the region was much close to the phosphorylationsite, while it was far from the phosphorylation site in the IP3R-II. This result indicatedthat the interaction of IP3R-I with IRAG spatially did not permit PKA to access tophosphorylation site.