Inositol 1,4,5-triphosphate-associated cGMP kinase substrate

Abstract

Inositol 1, 4, 5-trisphosphate (IP3) receptor associated cyclic GMP (cGMP) kinase substrate (IRAG, also known as Mrv1) is a type-2 integral membrane endoplasmic reticulum (ER) protein, which interacts with IP3 Receptor type 1 (IP3R1), cGMP kinase I-β (cGKI β) and other associated proteins. It plays a key role in NO, cGMP, and cGKI β mediated inhibition of IP3R1 activity and thus relaxes smooth muscle tone and inhibits platelet aggregation. As a scaffolding protein Mrv1 maintains the conformation of a heteroprotein complex containing cGKI β, IP3R1 and other proteins and enables efficient activity of cGKI β within the complex. Increased expression of Mrv1 or IRAG in the absence of tumor related transcription factor in pancreatic cancer cells suggest that it might be involved in tumorigenesis. Downregulation of Mrv1 during megakaryocyte maturation indicates that it is involved in cell growth and differentiation.

IFN-γ

“…Expression of IRAG is found in the heart, lungs, liver, pancreas, smooth muscle, colon, small intestines, pancreas, trachea, hippocampus, nucleus motorius, and nucleus trigemini (Graham et al 2008). Perinuclear immunostaining and immunoprecipitation with resident ER proteins suggests IRAG localization to the ER membrane (Ammendola et al 2001;Fritsch et al 2004;Geiselhöringer et al 2004a;Schlossmann et al 2000;Shaughnessy et al 1999).…”