Pleckstrin Homology Domain Containing Family G, Member 2 (PLEKHG2)

PLEKHG2 was a G protein-activated guanine-nucleotide exchange factor (GEF), and an N-terminal region of PLEKHG2 interacted directly with G protein beta/gamma subunits. PLEKHG2 activated a reporter gene driven by a serum response element (SRE) in HEK293 cells, and coexpression of PLEKHG2 with beta/gamma subunits, but not alpha subunits, further increased transcription. Combined beta/gamma/PLEKHG2 expression induced activation of RAC and CDC42, but not RhoA. PLEKHG2 enhanced transcription of an activated acetylcholine M2 receptor (CHRM2), and enhancement required the interaction of the receptor with a pertussis-sensitive inhibitory G protein. PLEKHG2 is involved in G protein signaling and links inhibitory G protein-coupled receptors to RAC and CDC42 via direct interaction with G protein beta/gamma subunits.