Inositol 1,4,5-Trisphosphate Receptor Phosphorylation in Breast Cancer

The aim of this study was to establish the type(s) of inositol 1,4,5-trisphosphate receptors (IP3Rs) in T47D breast cancer cells that regulate intracellular calcium (Ca 2+ ) and whether they interact with cyclin (Cy), an important regulator of cyclin-dependent kinases (cdk), during cell cycle progression. Immunoblotting, immunoprecipitation, and pull-down assays were used to identify IP3R expression and interaction with Cy. The relative IP3R3 expression, as compared to IP3R1, was higher in these cells. Pull-down analysis showed that IP3R3 interacted with both CyA and CyB. The interaction with Cys and the phosphorylation of IP3Rs by Cy/cdk complexes provide a novel mechanism of regulating intracellular Ca 2+ release and Ca 2+ -dependent signaling events in breast cancer.