G-protein-signaling modulator 1 (GPSM1)

G-protein-signaling modulator 1 (GPSM1) is a cytosolic accessory protein that regulates G protein signaling independently of classical G protein-coupled receptors (GPCRs)[1][4]. It functions as a guanine nucleotide dissociation inhibitor (GDI) for Gαi/o subunits, keeping them in the GDP-bound state and modulating both the basal and stimulus-dependent activity of heterotrimeric G proteins[1][2]. GPSM1 is critical for various cellular processes, including the control of mitotic spindle orientation, asymmetric cell division, metabolic inflammation, and epithelial cell repair, particularly in the context of renal injury and polycystic kidney disease[1][2][3]. Loss or dysregulation of GPSM1 has been implicated in type 2 diabetes, obesity, and cystic kidney diseases, and GPSM1 is considered a promising accessory protein target for therapeutic intervention in these disorders[2][3]. Experimental inhibitors of GPSM1 are under investigation for their potential to modulate inflammatory states and metabolic dysfunction[3].

Other names

Activator of G-protein signaling 3AGS3DKFZP727I051AGS3 homolog (C. elegans)G-protein-signalling modulator 1 (AGS3-like, C. elegans)G protein signaling modulator 1

Inhibition of GPSM1 can suppress pro-inflammatory phenotype in macrophages[3]; Modulation of G-protein βγ subunits to regulate downstream effectors[2]; Influences cAMP/PKA/CREB-mediated transcription factors and NF-κB pathway (in immune cells)[3]