Inositol 1,4,5-Trisphosphate Receptors as Signal Integrators

▪ Abstract The inositol 1,4,5 trisphosphate (IP 3 ) receptor (IP 3 R) is a Ca 2+ release channel that responds to the second messenger IP 3 . Exquisite modulation of intracellular Ca 2+ release via IP 3 Rs is achieved by the ability of IP 3 R to integrate signals from numerous small molecules and proteins including nucleotides, kinases, and phosphatases, as well as nonenzyme proteins. Because the ion conduction pore composes only ∼5% of the IP 3 R, the great bulk of this large protein contains recognition sites for these substances. Through these regulatory mechanisms, IP 3 R modulates diverse cellular functions, which include, but are not limited to, contraction/excitation, secretion, gene expression, and cellular growth. We review the unique properties of the IP 3 R that facilitate cell-type and stimulus-dependent control of function, with special emphasis on protein-binding partners.