Rho Guanine nucleotide exchange factor 7 from MyBioSource.com

Leucine rich repeat kinase 2 (LRKK2) is a multi-domain protein kinase, mutation in this gene are common cause of familial and sporadic Parkinson's disease. The LRKK2 exhibit low over all GTPase and kinase activity in vitro. Several proteins interact with LRKK2 to restore its kinase and GTPase activity, mainly Rho-guanine nucleotide-exchange factor 7 (ARHGEF7) and small GTPase CDC42. Interaction of ARHGEF7 with full length LRRK2 increased its GTPase activity. LRKK2 phosphorylates ARHGEF7 at previously unknown phosphorylation sites (1). The phosphorylation of ARHGEF7 led to feedback control mechanism for LRRK2 activity and also impact on the actin cytoskeleton regulation. Proteins of the p21-activated kinase (Pak) family are implicated in the regulation of gene expression, cytoskeletal architecture and apoptosis. Two closely related Pak3 binding proteins, p50 and ARHGEF7/p85 both arising from alternate splicing, have Src homology 3 domain that interact with Pak3 and Dbl homology and pleckstrin homology domain (2).

Rho-family GTPase are key regulators of the actin cytoskeleton and play a key role in in orchestrating and development and remodeling the synapse and spines (3). Aberrant signaling of GTPase can cause defect in spine density and cognitive impairments. The Rho-GTPase activity is activated by guanine nucleotide exchange factor (GEFs) and inhibited by GTPase-activating proteins (GAP). ARHGEF7, a GEF in conjunction with CaMKK and CaMKI, and GIT1 complex regulate the hippocampal plasticity and spinogenesis by activating the GTPase activity. ARHGEF7 phosphorylation at Ser516 enhances the GEF activity resulting in activation of Rac1, an established enhancer of spinogenesis (3). ARHGEF7 acts as GEF and Ca-induce membrane ruffling and promote cell migration, attachment and cell spreading. The ARHGEF interacts with Pak kinases thru the SH3 domains. The ARHGEF also interacts with GIT1, TGFB1, PTK2, FAK1, RAC1, ITCH and PARVB kinases and control cell cycle and apoptosis (4). The ARHGEF7 is expressed in 3 isoforms of varying length.

The ARHGEF7-selective antibodies were generated against synthetic peptide taken from near the carboxyl-terminal of the protein. The epitope is common in several other species. ARHGEF7 antibodies are affinity purified over immobilized antigen based chromatography, and the purified immunoglobulins are stabilized in antibody stabilization buffer for long-term storage. The anti-RASGRF-selective antibodies are fully characterized for applications in western blotting and ELISA at the recommended dilutions