Mechanistic pathways and biological roles for receptor-independent activators of G-protein signaling.
Signal processing via heterotrimeric G-proteins in response to cell surface receptors is a central and much investigated aspect of how cells integrate cellular stimuli to produce coordinated biological responses. The system is a target of numerous therapeutic agents and plays an important role in adaptive processes of organs; aberrant processing of signals through these transducing systems is a component of various disease states. In addition to G-protein coupled receptor (GPCR)-mediated activation of G-protein signaling, nature has evolved creative ways to manipulate and utilize the Galphabetagamma heterotrimer or Galpha and Gbetagamma subunits independent of the cell surface receptor stimuli. In such situations, the G-protein subunits (Galpha and Gbetagamma) may actually be complexed with alternative binding partners independent of the typical heterotrimeric Galphabetagamma. Such regulatory accessory proteins include the family of regulator of G-protein signaling (RGS) proteins that accelerate the GTPase activity of Galpha and various entities that influence nucleotide binding properties and/or subunit interaction. The latter group of proteins includes receptor-independent activators of G-protein signaling (AGS) proteins that play surprising roles in signal processing. This review provides an overview of our current knowledge regarding AGS proteins. AGS proteins are indicative of a growing number of accessory proteins that influence signal propagation, facilitate cross talk between various types of signaling pathways, and provide a platform for diverse functions of both the heterotrimeric Galphabetagamma and the individual Galpha and Gbetagamma subunits.
Blumer
Joe B
JB
Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, 1901 Perdido Street, New Orleans, LA 70112, United States.
Smrcka
Alan V
AV
Lanier
Stephen M
SM
D044385:GTP-Binding Protein alpha Subunits / Q000187:drug effects / Q000378:metabolism*; D044387:GTP-Binding Protein beta Subunits / Q000187:drug effects / Q000378:metabolism*; D044388:GTP-Binding Protein gamma Subunits / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D009711:Nucleotides / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D015398:Signal Transduction / Q000187:drug effects*
D044385:GTP-Binding Protein alpha Subunits; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D009711:Nucleotides; D043562:Receptors, G-Protein-Coupled