G-protein signaling modulator 1 (GPSM1) (GPSM1)

G-protein signaling modulator 1 (GPSM1), also known as Activator of G-protein signaling 3 (AGS3), is a critical regulatory protein that modulates G-protein-coupled receptor (GPCR) signaling pathways through a receptor-independent mechanism (UniProt Q86YR5). It contains four GoLoco motifs that specifically bind to the GDP-bound form of G-alpha-i subunits, acting as a guanine nucleotide dissociation inhibitor (GDI) (PMID: 10521335). By sequestering G-alpha-i-GDP, GPSM1 prevents its re-association with G-beta-gamma subunits, thereby prolonging G-beta-gamma-mediated signaling and inhibiting G-alpha-i-mediated inhibition of adenylyl cyclase (PMID: 11459833). Biologically, GPSM1 is involved in diverse processes such as spindle orientation during asymmetric cell division, macroautophagy, and the regulation of insulin secretion in pancreatic beta cells (PMID: 20639557, PMID: 25635391). In clinical contexts, dysregulation of GPSM1 has been implicated in the progression of various cancers, including glioblastoma and breast cancer, as well as in metabolic and neurodegenerative diseases (PMID: 32853456). Although no FDA-approved drugs currently target GPSM1, it is an area of active research for the development of small molecules or peptides that can modulate G-protein signaling in pathological states (PMID: 24107127).

Other names

Activator of G-protein signaling 3AGS3PAGS3

Acts as a guanine nucleotide dissociation inhibitor (GDI) for G-alpha-i subunits, stabilizing the GDP-bound state and preventing re-association with G-beta-gamma subunits.