Regulator of G-protein signaling 2 (RGS2)

Regulator of G-protein signaling 2 (RGS2) is a member of the RGS family of proteins that act as GTPase-activating proteins for certain G protein α subunits, notably Gαq and, in specific settings, Gαi. RGS2 accelerates GTP hydrolysis, thereby terminating G protein–coupled receptor signals. It is dynamically upregulated by neuronal activity and certain drugs, functioning as an immediate early gene in the brain[1]. RGS2 is implicated in modulating neuronal synaptic plasticity, regulating the magnitude and duration of signaling through several GPCR pathways, notably muscarinic acetylcholine receptors and adrenergic receptors[1][2][3]. In the cardiovascular system, RGS2 inhibits maladaptive signaling pathways that lead to cardiac hypertrophy and arrhythmias and is considered cardioprotective. Its dysfunction or altered expression has been implicated in cardiovascular diseases, certain psychiatric or neurological disorders, and potentially in cancer due to its influence on cellular growth and signaling[2][1]. There are presently no approved drugs that directly and selectively target RGS2, but it is a recognized regulator and potential biomarker within major signal transduction pathways[2].

Other names

Regulator of G-protein signaling 2RGS2G0S8GIG31Cell growth-inhibiting gene 31 proteinG0/G1 switch regulatory protein 8Cell growth-inhibiting protein 3124kDa protein

Drugs that change GPCR activity can alter RGS2 expression/activity indirectly. RGS2 itself acts as a GTPase-activating protein, accelerating inactivation of Gαq and certain Gαi subunits, thus dampening downstream signaling[1][2][3]. By modulating G protein signaling, drugs affecting upstream GPCRs (muscarinic, adrenergic) alter pathways including MAPK/ERK activation and intracellular calcium[1][2][3].