%0 Journal Article %A Joe B. Blumer %A Stephen M Lanier %T Activators of G-protein Signaling Exhibit Broad Functionality and Define a Distinct Core Signaling Triad %D 2013 %R 10.1124/mol.113.090068 %J Molecular Pharmacology %P mol.113.090068 %X Activators of G-protein signaling (AGS), initially discovered in the search for receptor-independent activators of G-protein signaling, define a broad panel of biological regulators that influence signal transfer from receptor to G-protein, guanine nucleotide binding and hydrolysis, G-protein subunit interactions and/or serve as alternative binding partners for Gα and Gβγ independent of the classical heterotrimeric Gβγ. AGS proteins generally fall into three groups based upon their interaction with and regulation of G-protein subunits: Group I - guanine nucleotide exchange factors (GEF), Group II - guanine nucleotide dissociation inhibitors, Group III - bind to Gβγ. Group I AGS proteins may engage all subclasses of G-proteins, whereas Group II AGS proteins primarily engage the Gi/Go/transducin family of G-proteins. A fourth group of AGS proteins, with selectivity for Gα16 may be defined by the Mitf-Tfe family of transcription factors. Groups I-III may act in concert generating a core signaling triad analogous to the core triad for heterotrimeric G-proteins (GEF - G-proteins - Effector). These two core triads may function independently of each other or actually cross-integrate for additional signal processing. AGS proteins have broad functional roles and their discovery has advanced new concepts in signal processing, cell and tissue biology, receptor pharmacology and system adaptation providing unexpected platforms for therapeutic and diagnostic development. %U https://molpharm.aspetjournals.org/content/molpharm/early/2013/12/03/mol.113.090068.full.pdf