Schlossmann, Jens and Desch, Matthias (2011) IRAG and novel PKG targeting in the cardiovascular system. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 301 (3). H672-H682. ISSN 0363-6135
Full text not available from this repository. (Request a copy)Abstract
Signaling by nitric oxide (NO) determines several cardiovascular functions including blood pressure regulation, cardiac and smooth muscle hypertrophy, and platelet function. NO stimulates the synthesis of cGMP by soluble guanylyl cyclases and thereby activates cGMP-dependent protein kinases (PKGs), mediating most of the cGMP functions. Hence, an elucidation of the PKG signaling cascade is essential for the understanding of the (patho)physiological aspects of NO. Several PKG signaling pathways were identified, meanwhile regulating the intracellular calcium concentration, mediating calcium desensitization or cytoskeletal rearrangement. During the last decade it emerged that the inositol trisphosphate receptor-associated cGMP-kinase substrate (IRAG), an endoplasmic reticulum-anchored 125-kDa membrane protein, is a main signal transducer of PKG activity in the cardiovascular system. IRAG interacts specifically in a trimeric complex with the PKG1 beta isoform and the inositol 1,4,5-trisphosphate receptor I and, upon phosphorylation, reduces the intracellular calcium release from the intracellular stores. IRAG motifs for phosphorylation and for targeting to PKG1 beta and 1,4,5-trisphosphate receptor I were identified by several approaches. The (patho)physiological functions for the regulation of smooth muscle contractility and the inhibition of platelet activation were perceived. In this review, the IRAG recognition, targeting, and function are summarized compared with PKG and several PKG substrates in the cardiovascular system.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | DEPENDENT PROTEIN-KINASE; VASCULAR SMOOTH-MUSCLE; LIGHT-CHAIN PHOSPHATASE; INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; GTPASE-ACTIVATING PROTEIN; CA2+-ACTIVATED K+ CHANNEL; BLOOD-PRESSURE REGULATION; CYSTEINE-RICH PROTEIN-2; LEUCINE-ZIPPER MOTIF; LIM-ONLY PROTEIN; inositol trisphosphate receptor-associated guanosine 3 ',5 '-cyclic monophosphate-kinase substrate substrate; nitric oxide; guanosine 3 ',5 '-cyclic monophosphate-dependent protein kinase |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Pharmacology and Toxicology (Prof. Schlossmann, formerly Prof. Seifert) |
| Depositing User: | Petra Gürster |
| Date Deposited: | 05 May 2020 06:59 |
| Last Modified: | 05 May 2020 06:59 |
| URI: | https://pred.uni-regensburg.de/id/eprint/20186 |
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