Activates Rho-GTPases by promoting the exchange of GDP for GTP. May be involved in epithelial barrier permeability, cell motility and polarization, dendritic spine morphology, antigen presentation, leukemic cell differentiation, cell cycle regulation, and cancer. Binds Rac-GTPases, but does not seem to promote nucleotide exchange activity toward Rac-GTPases, which was uniquely reported in PubMed:9857026. May stimulate instead the cortical activity of Rac. Inactive toward CDC42, TC10, or Ras-GTPases. Forms an intracellular sensing system along with NOD1 for the detection of microbial effectors during cell invasion by pathogens. Required for RHOA and RIP2 dependent NF-kappaB signaling pathways activation upon S.flexneri cell invasion. Involved not only in sensing peptidoglycan (PGN)-derived muropeptides through NOD1 that is independent of its GEF activity, but also in the activation of NF-kappaB by Shigella effector proteins (IpgB2 and OspB) which requires its GEF activity and the activation of RhoA.
The DH (DBL-homology) domain interacts with and promotes loading of GTP on RhoA. The PH (pleckstrin-homology) domain is involved in microtubule binding and targeting to tight junctions.
Phosphorylation of Ser-886 by PAK1 induces binding to protein 14-3-3 zeta, promoting its relocation to microtubules and the inhibition of its activity. Phosphorylated by STK6 and CDK1 during mitosis, which negatively regulates its activity. Phosphorylation by MAPK1 or MAPK3 increases nucleotide exchange activity. Phosphorylation by PAK4 releases GEF-H1 from the microtubules.
Cytoplasm. Cell junction > tight junction. Golgi apparatus. Cytoplasm > cytoskeleton > spindle. Cell projection > ruffle membrane. Localizes to the tips of cortical microtubules of the mitotic spindle during cell division, and is further released upon microtubule depolymerization. Recruited into membrane ruffles induced by S.flexneri at tight junctions of polarized epithelial cells.
Immunocytochemistry/ Immunofluorescence - Anti-GEF H1 antibody (ab155785)Image is courtesy of an AbReview submitted by Dr Armen Petrosyan.
Immunocytochemical immunofluorescence analysis of formaldehyde-fixed human HepG2 cells, labelling GEF H1 with ab155785 with a dilution of 1/50 incubated for 3 hours at 22°C in 1% donkey serum in 0.1% PBST diluent. Permeablization with 0.2% Triton X-100. Blocking was with 1% donkey serum in 0.1% PBST incubated for 1 hour at 22°C. Secondary was a donkey anti-rabbit polyclonal Alexa Fluor® 594 at 1/200. Counterstain is DAPI (blue) against nuclear DNA.