Bcl-2 and IP₃ compete for the ligand-binding domain of IP₃Rs modulating Ca²⁺ signaling output.

ABSTRACT: Bcl-2 proteins have emerged as critical regulators of intracellular Ca²⁺ dynamics by directly targeting and inhibiting the IP₃ receptor (IP₃R), a major intracellular Ca²⁺-release channel. Here, we demonstrate that such inhibition occurs under conditions of basal, but not high IP₃R activity, since overexpressed and purified Bcl-2 (or its BH4 domain) can inhibit IP₃R function provoked by low concentration of agonist or IP₃, while fails to attenuate against high concentration of agonist or IP₃. Surprisingly, Bcl-2 remained capable of inhibiting IP₃R1 channels lacking the residues encompassing the previously identified Bcl-2-binding site (a.a. 1380-1408) located in the ARM2 domain, part of the mo

SUBMITTER: Ivanova H 

PROVIDER: S-EPMC11105292 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature