Many cellular processes require the release of calcium from IP3-sensitive intracellular stores. In smooth muscle, calcium release from the endoplasmic reticulum is inhibited by a cGMP-activated kinase called cGKI, which also phosphorylates the IP3 receptor (IP3R). Schlossmann et al. report that cGKI is in a complex with the IP3R and a newly identified substrate called IP3R-associated cGMP kinase substrate (IRAG). IRAG is predicted to be membrane-associated. When overexpressed in cultured cells in the presence of cGMP, IRAG and cGKI inhibited calcium mobilization in reponse to an IP3-generating stimulus. The authors propose that IP3-mediated calcium release is regulated by the cGKI-dependent phosphorylation of IRAG and that IRAG may modulate IP3R function.
Schlossmann, J., Ammendola, A., Ashman, K., Zong, X., Huber, A., Neubauer, G., Wang, G-X., Allescher, H-D., Korth, M., Wilm, M., Hofmann, F., and Ruth, P. (2000) Regulation of intracellular calcium by a signalling complex of IRAG, IP3 receptor and cGMP kinase Iβ. Nature 404: 197-201. [Online Journal]