[PDF][PDF] IRBIT suppresses IP3 receptor activity by competing with IP3 for the common binding site on the IP3 receptor
Molecular cell, 2006•cell.com
Summary The inositol 1, 4, 5-trisphosphate (IP 3) receptors (IP 3 Rs) are IP 3-gated
intracellular Ca 2+ channels. We previously identified an IP 3 R binding protein, IRBIT,
which binds to the IP 3 binding domain of IP 3 R and is dissociated from IP 3 R in the
presence of IP 3. In the present study, we showed that IRBIT suppresses the activation of IP
3 R by competing with IP 3 by [3 H] IP 3 binding assays, in vitro Ca 2+ release assays, and
Ca 2+ imaging of intact cells. Multiserine phosphorylation of IRBIT was essential for the …
intracellular Ca 2+ channels. We previously identified an IP 3 R binding protein, IRBIT,
which binds to the IP 3 binding domain of IP 3 R and is dissociated from IP 3 R in the
presence of IP 3. In the present study, we showed that IRBIT suppresses the activation of IP
3 R by competing with IP 3 by [3 H] IP 3 binding assays, in vitro Ca 2+ release assays, and
Ca 2+ imaging of intact cells. Multiserine phosphorylation of IRBIT was essential for the …
Summary
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.
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