|
 |
IRAG and Novel PKG Targeting in the cardiovascular system
J Schlossmann... - American Journal of Physiology- ..., 2011 - Am Physiological Soc Signalling by nitric oxide (NO) determines several cardiovascular functions including blood 25
... IRAG interacts specifically in a trimeric complex with the PKG1β isoform and the inositol 35
... 1,4,5-trisphosphate receptor I (IP3RI) and upon phosphorylation reduces the ...
Signalling by nitric oxide (NO) determines several cardiovascular functions including blood pressure regulation, cardiac and smooth muscle hypertrophy and platelet function. NO stimu-lates the synthesis of c GMP by soluble guanylyl cyclases and thereby activates c GMP-dependent protein kinases (PKG) mediating most of the c GMP-functions. Hence, elucidation of the PKG signalling cascade is essential for the understanding of the (patho)physiological aspects of NO. Several PKG signalling pathways were identified meanwhile regulating the intracellular calcium concentration, mediating calcium desensitization or cytoskeletal rear-rangement. During the last decade it emerged that the inositol-trisphosphate receptor-associated c GMP-kinase substrate (IRAG), an endoplasmic reticulum anchored 125 k Da membrane protein, is a main signal transducer of PKG activity in the cardiovascular system. IRAG interacts specifically in a trimeric complex with the PKG1β isoform and the inositol 1,4,5-trisphosphate receptor I (IP3RI) and upon phosphorylation reduces the intracellular calcium release from the intracellular stores. IRAG motifs for phosphorylation and for targeting to PKG1β and IP3RI were identified by several approaches. The (patho)physiological functions for regulation of smooth muscle contractility and inhibition of platelet activation were perceived. In this review, the IRAG recognition, targeting and function is summarized in comparision to PKG and several PKG substrates in the cardiovascular system.
More Details:
IRAG and Novel PKG Targeting in the cardiovascular system |
|
|
