Pleckstrin homology domain-containing family G member 2 (PLEKHG2)

PLEKHG2 is a large multidomain signaling protein (about 1300 amino acids, 130 kDa) that functions as a guanine nucleotide exchange factor (GEF) mainly for the Rho family GTPases Rac1 and Cdc42, with recognized roles in regulating actin polymerization and cell morphology. It is activated by direct interaction with the beta and gamma subunits of heterotrimeric G proteins downstream of G protein-coupled receptors, enabling key cellular processes such as chemotaxis and cell motility. PLEKHG2 is implicated in the development and maintenance of neuronal structures, including axons, dendrites, and synaptic spines, with mutations (esp. Arg204Trp) causing severe neurodevelopmental disorders such as microcephaly, intellectual disability, and dystonia. It also has oncogenic potential, particularly in leukemias. Protein interactions include Gβγ, β-actin, FHL1, and Gαs, and it is subject to regulation by phosphorylation via signals such as SRC and EGFR. The precise physiological role and therapeutic targeting strategies remain under investigation.

Other names

ARHGEF42CLGLDAMDFLJ00018CTB-60E11.4common-site lymphoma/leukemia guanine nucleotide exchange factorPH domain-containing family G member 2pleckstrin homology and RhoGEF domain containing G2