Biological Description

Specificity Phospho-GEF-H1 (Ser886) Antibody [E24J19] detects endogenous levels of total GEF-H1 protein only when it is phosphorylated at Ser886.
Background Phospho-GEF-H1 at Ser886 denotes the activated conformation of guanine nucleotide exchange factor H1 (GEF-H1/ARHGEF2), a DH-PH domain RhoA-specific GEF that cycles between microtubule-associated inhibition and cytoplasmic activation to drive actin dynamics and contractility. GEF-H1 possesses an N-terminal microtubule-binding C1 domain, central DH-PH GEF module catalyzing GDP/GTP exchange on RhoA, and C-terminal coiled-coil and 14-3-3 binding motifs including the RSLS motif harboring Ser886. Phosphorylation at Ser886 by Par1b/MARK2 kinase disrupts microtubule binding, releasing GEF-H1 into the cytoplasm where it engages RhoA to promote stress fiber formation, focal adhesion maturation, and actomyosin contractility; conversely, PP2A-mediated dephosphorylation restores microtubule association for sequestration. During cytokinesis, mitotic kinases like Aurora B phosphorylate Ser886 to localize GEF-H1 at the cleavage furrow, activating cortical RhoA for equatorial constriction and membrane ingression independent of centralspindlin-Ect2. Tight junction cingulin binds and inhibits GEF-H1 RhoGEF activity to maintain epithelial barrier integrity, while FcεRI signaling in mast cells activates it for granule exocytosis. Par1b targets three conserved serines near the C1 domain (including Ser886), converting dynamic microtubule turnover to stabilization in protrusions for cell polarization. Phospho-Ser886 GEF-H1 coordinates microtubule depolymerization with RhoA-mediated cytoskeletal remodeling in migration, division, and barrier function. Dysregulation promotes invasion in carcinomas and disrupts polarity in neurological disorders.

Usage Information

Application WB Dilution
WB
1:1000
Reactivity Human, Mouse, Rat
Source Rabbit Monoclonal Antibody MW 120 kDa
Storage Buffer PBS, pH 7.2+50% Glycerol+0.05% BSA+0.01% NaN3
Storage
(from the date of receipt)
-20°C (avoid freeze-thaw cycles), 2 years

References

  • https://pubmed.ncbi.nlm.nih.gov/21513698/
  • https://pubmed.ncbi.nlm.nih.gov/17488622/

Application Data