Suppression of IP3-mediated calcium release and apoptosis by Bcl-2 involves the participation of protein phosphatase 1.
The involvement and potential interdependence of inositol trisphosphate (IP3) receptors and Bcl-2 in the regulation of Ca2+ signaling is not clear. Here, we have explored the mechanism(s) of how Bcl-2 suppresses the IP3-sensitive Ca2+ release in MCF-7 cells focusing on the possible role of protein phosphatase 1 (PP1). We found that through influences on protein-protein interaction, Bcl-2 may alter the balance between the effects of phosphatase (PP1) and kinase (PKA) on the IP3 R1 signaling complex. Using various experimental approaches including phosphatase inhibition and RNAi, we show that Bcl-2 by competing with IP3R1 for the binding of PP1 can reduce the IP3-mediated calcium signal and protect cells from mitochondrial dysfunction and cell death.
Xu
Liping
L
Department of Pathology, Wayne State University School of Medicine, 540 E. Canfield, Detroit, MI 48201, USA.
Kong
Dejuan
D
Zhu
Liping
L
Zhu
Weijia
W
Andrews
David W
DW
Kuo
Tuan H
TH
D000255:Adenosine Triphosphate / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D020013:Calcium Signaling / Q000187:drug effects*; D003587:Cytomegalovirus; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology*; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D054645:Protein Phosphatase 1; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*
D004791:Enzyme Inhibitors; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D019253:Proto-Oncogene Proteins c-bcl-2; D015544:Inositol 1,4,5-Trisphosphate; D000255:Adenosine Triphosphate; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1