PMID- 21268094 OWN - NLM STAT- MEDLINE DCOM- 20110503 LR - 20211203 IS - 1097-4644 (Electronic) IS - 0730-2312 (Linking) VI - 112 IP - 2 DP - 2011 Feb TI - Positive regulation of inositol 1,4,5-trisphosphate-induced Ca2+ release by mammalian target of rapamycin (mTOR) in RINm5F cells. PG - 723-33 LID - 10.1002/jcb.23006 [doi] AB - The inositol 1,4,5-trisphosphate receptor (IP(3)R), a ligand-gated Ca(2+) channel, is the main regulator of intracellular Ca(2+) mobilization in non-excitable cells. An emerging body of evidence suggests that specific regulatory control of the Ca(2+) signaling pathway is modulated by the activation of additional signaling pathways. In the present study, we investigated the influence of the PI3-kinase/mammalian target of rapamycin (mTOR) pathway on the activity of the IP(3)R/Ca(2+) signaling pathway in RINm5F cells. We used a co-immunoprecipitation approach to show that mTOR physically interacts with IP(3)R-3 in an mTOR activity-dependent manner. We also showed that IP(3)R is phosphorylated by mTOR in cellulo. All the conditions known to modulate mTOR activity (IGF-1, wortmannin, rapamycin, PP242, and nutrient starvation) were shown to modify carbachol-induced Ca(2+) signaling in RINm5F cells. Lastly, we used an assay that directly measures the activity of IP(3)R, to show that mTOR increases the apparent affinity of IP(3)R. Given that mTOR controls cell proliferation and cell homeostasis, and that Ca(2+) plays a key role in these two phenomena, it follows that mTOR facilitates IP(3)R-mediated Ca(2+) release when the nutritional status of cells requires it. CI - Copyright (c) 2011 Wiley-Liss, Inc. FAU - Fregeau, Marc-Olivier AU - Fregeau MO AD - Faculty of Medicine and Health Sciences, Department of Pharmacology, Universite de Sherbrooke, Sherbrooke, Quebec, Canada. FAU - Regimbald-Dumas, Yannik AU - Regimbald-Dumas Y FAU - Guillemette, Gaetan AU - Guillemette G LA - eng GR - Canadian Institutes of Health Research/Canada PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Cell Biochem JT - Journal of cellular biochemistry JID - 8205768 RN - 0 (Inositol 1,4,5-Trisphosphate Receptors) RN - 85166-31-0 (Inositol 1,4,5-Trisphosphate) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - SY7Q814VUP (Calcium) SB - IM MH - Animals MH - Blotting, Western MH - Calcium/*metabolism MH - Cell Line, Tumor MH - Immunoprecipitation MH - Inositol 1,4,5-Trisphosphate/*pharmacology MH - Inositol 1,4,5-Trisphosphate Receptors/metabolism MH - Phosphorylation MH - Protein Binding MH - Rats MH - TOR Serine-Threonine Kinases/*metabolism EDAT- 2011/01/27 06:00 MHDA- 2011/05/04 06:00 CRDT- 2011/01/27 06:00 PHST- 2011/01/27 06:00 [entrez] PHST- 2011/01/27 06:00 [pubmed] PHST- 2011/05/04 06:00 [medline] AID - 10.1002/jcb.23006 [doi] PST - ppublish SO - J Cell Biochem. 2011 Feb;112(2):723-33. doi: 10.1002/jcb.23006.