IP3受体结合蛋白通过与IP3竞争IP3受体上的共同结合位点来抑制IP3受体活性。
IRBIT suppresses IP3 receptor activity by competing with IP3 for the common binding site on the IP3 receptor.
作者信息
Ando Hideaki, Mizutani Akihiro, Kiefer Hélène, Tsuzurugi Dai, Michikawa Takayuki, Mikoshiba Katsuhiko
机构信息
Laboratory for Developmental Neurobiology, Brain Science Institute, RIKEN, Saitama 351-0198.
Division of Molecular Neurobiology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639.
出版信息
Mol Cell. 2006 Jun 23;22(6):795-806. doi: 10.1016/j.molcel.2006.05.017.
The inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs) are IP3-gated intracellular Ca2+ channels. We previously identified an IP3R binding protein, IRBIT, which binds to the IP3 binding domain of IP3R and is dissociated from IP3R in the presence of IP3. In the present study, we showed that IRBIT suppresses the activation of IP3R by competing with IP3 by [3H]IP3 binding assays, in vitro Ca2+ release assays, and Ca2+ imaging of intact cells. Multiserine phosphorylation of IRBIT was essential for the binding, and 10 of the 12 key amino acids in IP3R for IP3 recognition participated in binding to IRBIT. We propose a unique mode of IP3R regulation in which IP3 sensitivity is regulated by IRBIT acting as an endogenous "pseudoligand" whose inhibitory activity can be modulated by its phosphorylation status.
肌醇1,4,5-三磷酸（IP3）受体（IP3Rs）是IP3门控的细胞内Ca2+通道。我们之前鉴定出一种IP3R结合蛋白IRBIT，它与IP3R的IP3结合结构域结合，并在IP3存在时从IP3R上解离。在本研究中，我们通过[3H]IP3结合试验、体外Ca2+释放试验和完整细胞的Ca2+成像表明，IRBIT通过与IP3竞争来抑制IP3R的激活。IRBIT的多丝氨酸磷酸化对于结合至关重要，并且IP3R中参与IP3识别的12个关键氨基酸中的10个参与了与IRBIT的结合。我们提出了一种独特的IP3R调节模式，其中IP3敏感性由作为内源性“假配体”的IRBIT调节，其抑制活性可由其磷酸化状态调节。
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