Regulator of G protein signaling 14 (RGS14)

Regulator of G protein signaling 14 (RGS14) is a multifunctional intracellular signaling protein characterized by a unique domain architecture, including a canonical RGS domain, tandem Ras-binding domains (RBDs), and a GoLoco (G protein regulatory) motif[1][3][4]. RGS14 acts primarily as a GTPase activating protein (GAP) for Gαi/o subunits, accelerating GTP hydrolysis and terminating G protein-coupled receptor (GPCR) signaling[1][3]. Additionally, RGS14 can act as a molecular scaffold, coordinating integrated signaling via G proteins and the MAPK/ERK pathway by binding active H-Ras and assembling multiprotein complexes with Raf and ERK kinases[2][3]. RGS14 is highly expressed in specific brain regions, notably hippocampal pyramidal neurons (especially CA2), the striatum, amygdala, and is implicated in suppressing synaptic plasticity, regulating long-term potentiation, and thus modulating learning and memory[1][2][4][5]. Alternative splice variants, including a nuclear-localized form, exist and may have unique functions, particularly in primate brain[4]. While no drugs are currently known to directly interact with RGS14, its role in neurological processes makes it a potential target for diseases affecting cognition and synaptic function[2][5].

Other names

Regulator of G-protein signalling 14RGS14regulator of G-protein signaling 14RGS14-S (for a splice variant)RGS14 gene product

RGS14 acts as a GTPase activating protein (GAP) for Gαi/o subunits, increasing GTP hydrolysis to terminate G protein signaling. It also functions as a scaffold for assembling multiprotein complexes involving G proteins, H-Ras, Raf, MEK, and ERK, integrating G protein and MAPK/ERK signaling. Additionally, RGS14 is a guanine nucleotide dissociation inhibitor (GDI) for Gαi1 and Gαi3 subunits.