Bcl-2 functionally interacts with inositol 1,4,5-trisphosphate receptors to regulate calcium release from the ER in response to inositol 1,4,5-trisphosphate |
| |
Authors: | Chen Rui Valencia Ignacio Zhong Fei McColl Karen S Roderick H Llewelyn Bootman Martin D Berridge Michael J Conway Stuart J Holmes Andrew B Mignery Gregory A Velez Patricio Distelhorst Clark W |
| |
Affiliation: | Department of Medicine, Comprehensive Cancer Center, Case Western Reserve University and University Hospitals of Cleveland, OH 44106, USA. |
| |
Abstract: | Inositol 1,4,5-trisphosphate (InsP3) receptors (InsP3Rs) are channels responsible for calcium release from the endoplasmic reticulum (ER). We show that the anti-apoptotic protein Bcl-2 (either wild type or selectively localized to the ER) significantly inhibited InsP3-mediated calcium release and elevation of cytosolic calcium in WEHI7.2 T cells. This inhibition was due to an effect of Bcl-2 at the level of InsP3Rs because responses to both anti-CD3 antibody and a cell-permeant InsP3 ester were decreased. Bcl-2 inhibited the extent of calcium release from the ER of permeabilized WEHI7.2 cells, even at saturating concentrations of InsP3, without decreasing luminal calcium concentration. Furthermore, Bcl-2 reduced the open probability of purified InsP3Rs reconstituted into lipid bilayers. Bcl-2 and InsP3Rs were detected together in macromolecular complexes by coimmunoprecipitation and blue native gel electrophoresis. We suggest that this functional interaction of Bcl-2 with InsP3Rs inhibits InsP3R activation and thereby regulates InsP3-induced calcium release from the ER. |
| |
Keywords: | InsP3 receptor calcium signaling apoptosis calcium channel T cell receptor |
本文献已被 PubMed 等数据库收录! |
|