Phosphorylation of inositol 1,4,5-trisphosphate receptors by protein kinase B/Akt inhibits Ca2+ release and apoptosis.

ABSTRACT: Imbalance of signals that control cell survival and death results in pathologies, including cancer and neurodegeneration. Two pathways that are integral to setting the balance between cell survival and cell death are controlled by lipid-activated protein kinase B (PKB)/Akt and Ca(2+). PKB elicits its effects through the phosphorylation and inactivation of proapoptotic factors. Ca(2+) stimulates many prodeath pathways, among which is mitochondrial permeability transition. We identified Ca(2+) release through inositol 1,4,5-trisphosphate receptor (InsP(3)R) intracellular channels as a prosurvival target of PKB. We demonstrated that in response to survival signals, PKB interacts with and phosphorylates InsP(3)Rs, significantly reducing their Ca(2+) release activity. Moreover, phosphorylation

SUBMITTER: Szado T 

PROVIDER: S-EPMC2268153 | biostudies-literature | 2008 Feb

REPOSITORIES: biostudies-literature