Identification of a receptor-independent activator of G protein signaling (AGS8) in ischemic heart and its interaction with G beta gamma

Title

Identification of a receptor-independent activator of G protein signaling (AGS8) in ischemic heart and its interaction with G beta gamma

Creator

Sato M; Cismowski M J; Toyota E; Smrcka A V; Lucchesi P A; Chilian W M; Lanier S M

Publisher

Proceedings of the National Academy of Sciences of the United States of America

Date

2006
2006-01

Description

As part of a broader effort to identify postreceptor signal regulators involved in specific diseases or organ adaptation, we used an expression cloning system in Saccharomyces cerevisiae to screen cDNA libraries from rat ischemic myocardium, human heart, and a prostate leiomyosarcoma for entities that activated G protein signaling in the absence of a G protein coupled receptor. We report the characterization of activator of G protein signaling (AGS) 8 (KIAA1866), isolated from a rat heart model of repetitive transient ischemia. AGS8 mRNA was induced in response to ventricular ischemia but not by tachycardia, hypertrophy, or failure. Hypoxia induced AGS8 mRNA in isolated adult ventricular cardiomyocytes but not in rat aortic smooth muscle cells, endothelial cells, or cardiac fibroblasts, suggesting a myocyte-specific adaptation mechanism involving remodeling of G protein signaling pathways. The bioactivity of AGS8 in the yeast-based assay was independent of guanine nucleotide exchange by Ga, suggesting an impact on subunit interactions. Subsequent studies indicated that AGS8 interacts directly with G beta gamma and this occurs in a manner that apparently does not alter the regulation of the effector PLC-beta(2) by G beta gamma. Mechanistically, AGS8 appears to promote G protein signaling by a previously unrecognized mechanism that involves direct interaction with G beta gamma.

Subject

accessory protein; coronary collateral growth; drosophila ric-8; effectors; heterotrimeric g-proteins; hypoxia; localization; modulators; orientation; rat; Science & Technology - Other Topics; signal adaptation; spindle; subunits

Format

Journal Article

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Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

797-802

Issue

3

Volume

103

Citation

Sato M; Cismowski M J; Toyota E; Smrcka A V; Lucchesi P A; Chilian W M; Lanier S M, “Identification of a receptor-independent activator of G protein signaling (AGS8) in ischemic heart and its interaction with G beta gamma,” NEOMED Bibliography Database, accessed June 25, 2021, https://neomed.omeka.net/items/show/7004.

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