PT  - JOURNAL ARTICLE
AU  - Sjögren, Benita
AU  - Neubig, Richard R.
TI  - Thinking Outside of the “RGS Box”: New Approaches to Therapeutic Targeting of Regulators of G Protein Signaling
AID  - 10.1124/mol.110.065219
DP  - 2010 Oct 01
TA  - Molecular Pharmacology
PG  - 550--557
VI  - 78
IP  - 4
4099  - http://molpharm.aspetjournals.org/content/78/4/550.short
4100  - http://molpharm.aspetjournals.org/content/78/4/550.full
SO  - Mol Pharmacol2010 Oct 01; 78
AB  - Regulators of G protein signaling (RGS) proteins are emerging as potentially important drug targets. The mammalian RGS protein family has more than 20 members and they share a common ∼120-residue RGS homology domain or “RGS box.” RGS proteins regulate signaling via G protein-coupled receptors by accelerating GTPase activity at active α subunits of G proteins of the Gq and Gi/o families. Most studies searching for modulators of RGS protein function have been focused on inhibiting the GTPase accelerating protein activity. However, many RGS proteins contain additional domains that serve other functions, such as interactions with proteins or subcellular targeting. Here, we discuss a rationale for therapeutic targeting of RGS proteins by regulation of expression or allosteric modulation to permit either increases or decreases in RGS function. Several RGS proteins have reduced expression or function in pathophysiological states, so strategies to increase RGS function would be useful. Because several RGS proteins are rapidly degraded by the N-end rule pathway, finding ways to stabilize them may prove to be an effective way to enhance RGS protein function.