Mammalian target of rapamycin (mTOR) phosphorylates inositol 1,4,5-trisphosphate receptor type 2 and increases its Ca2+ release activity

2011 ◽  
Vol 23 (1) ◽  
pp. 71-79 ◽  
Author(s):  
Yannik Régimbald-Dumas ◽  
Marc-Olivier Frégeau ◽  
Gaétan Guillemette
Keyword(s):  
Mammalian Target Of Rapamycin ◽  
Receptor Type ◽  
Target Of Rapamycin ◽  
Inositol 1,4,5 Trisphosphate ◽  
Trisphosphate Receptor

scholarly journals Insulin Promotes the Association of Heat Shock Protein 90 with the Inositol 1,4,5-Trisphosphate Receptor to Dampen Its Ca2+ Release Activity

Endocrinology ◽  
2009 ◽  
Vol 150 (5) ◽  
pp. 2190-2196 ◽  
Author(s):  
Nathalie Nguyen ◽  
Nancy Francoeur ◽  
Valérie Chartrand ◽  
Klaus Klarskov ◽  
Gaétan Guillemette ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Protein Interactions ◽  
Mammalian Target Of Rapamycin ◽  
Src Kinase ◽  
Target Of Rapamycin ◽  
Resting Cells ◽  
Release Channel ◽  
Inositol 1,4,5 Trisphosphate ◽  
Trisphosphate Receptor

The inositol 1,4,5-trisphosphate receptor (IP3R) is a Ca2+ release channel that plays a pivotal role in regulating intracellular Ca2+ levels in resting cells. Three isoforms of IP3Rs have been identified, and they all possess a large regulatory domain that covers about 60% of the protein. This regulation is accomplished by interaction with small molecules, posttranslational modifications, and mostly protein-protein interactions. In our search for new binding partners of the IP3R, we found that 90-kDa heat-shock protein (Hsp90) binds to the IP3R. This interaction increased on stimulation of HEK293T6.11 cells with insulin but not with Gq protein-coupled receptor (GqPCR) agonists. Moreover, the Hsp90 inhibitor geldanamycin (GA) disrupted the interaction between Hsp90 and the IP3R. Pretreatment of HEK293T6.11 cells with GA greatly increased the intracellular Ca2+ release induced by a GqPCR agonist. Insulin alone did not induce any intracellular Ca2+ release. However, insulin diminished the intracellular Ca2+ release induced by a GqPCR agonist. Interestingly, GA abolished the inhibitory effect of insulin on GqPCR-induced intracellular Ca2+ release. Furthermore, in our search for a mechanistic explanation to this phenomenon, we found that inhibition of kinases activated downstream of the insulin receptor greatly increased the interaction between Hsp90 and the IP3R. Of greater interest, we found that the simultaneous inhibition of mammalian target of rapamycin and the Src kinase almost completely disrupted the interaction between Hsp90 and the IP3R. These results demonstrate that insulin promotes the interaction of Hsp90 with the IP3R to dampen its Ca2+ release activity by a complex mechanism involving mammalian target of rapamycin and the Src kinase.

539 Inositol 1,4,5-Trisphosphate Receptor Type 2 Modulates Bsep Activity in Hepatocytes

2010 ◽  
Vol 138 (5) ◽  
pp. S-791
Author(s):  
Emma A. Kruglov ◽  
Samir Gautam ◽  
Michael H. Nathanson
Keyword(s):  
Receptor Type ◽  
Inositol 1,4,5 Trisphosphate ◽  
Trisphosphate Receptor

scholarly journals Inositol 1,4,5-trisphosphate receptor type 2-independent Ca2+ release from the endoplasmic reticulum in astrocytes

Glia ◽  
2018 ◽  
Vol 67 (1) ◽  
pp. 113-124 ◽  
Author(s):  
Yohei Okubo ◽  
Kazunori Kanemaru ◽  
Junji Suzuki ◽  
Kenta Kobayashi ◽  
Kenzo Hirose ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Receptor Type ◽  
Inositol 1,4,5 Trisphosphate ◽  
Trisphosphate Receptor

Differential modulation of inositol 1,4,5-trisphosphate receptor type 1 and type 3 by ATP

Cell Calcium ◽  
2000 ◽  
Vol 27 (5) ◽  
pp. 257-267 ◽  
Author(s):  
K. Maes ◽  
L. Missiaen ◽  
P. De Smet ◽  
S. Vanlingen ◽  
G. Callewaert ◽  
...  
Keyword(s):  
Receptor Type ◽  
Differential Modulation ◽  
Inositol 1,4,5 Trisphosphate ◽  
Trisphosphate Receptor ◽  
Type 3
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