Rho guanine nucleotide exchange factor 2; guanine nucleotide exchange factor H1; GEF-H1; microtubule-regulated Rho-GEF; proliferating cell nucleolar antigen p40 (ARHGEF2, KIAA0651, LFP40)
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Function
- activates Rho-GTPases by promoting the exchange of GDP for GTP
- may be involved in
- epithelial barrier permeability
- cell motility & polarization
- dendritic spine morphology
- antigen presentation
- leukemic cell differentiation
- cell cycle regulation
- cancer
- binds Rac-GTPases, but does not seem to promote nucleotide exchange activity toward Rac-GTPases
- may stimulate the cortical activity of Rac
- inactive toward CDC42, TC10, or Ras-GTPases
- forms an intracellular sensing system along with NOD1 for detection of microbial effectors during cell invasion by pathogens
- required for RHOA & RIP2 dependent NF-kappaB signaling upon S flexneri cell invasion
- role in sensing peptidoglycan (PGN)-derived muropeptides through NOD1 independent of its GEF activity
- role in activation of NF-kappaB by Shigella effector proteins (IpgB2 & OspB) which requires its GEF activity & activation of RhoA
- phosphorylation of Ser-886 by PAK1 induces binding to protein 14-3-3 zeta, promoting its relocation to microtubules & inhibition of its activity
- phosphorylated by AURKA & 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
- interacts with 14-3-3 zeta when phosphorylated at Ser-886
- interacts with the kinases PAK4, AURKA & MAPK1
- interacts with RHOA & RAC1
- interacts with NOD1
- interacts (via the N-terminal Zn+2 finger) with CAPN6 (via domain II) (putative)
Structure
- the DH (DBL-homology) domain interacts with & promotes loading of GTP on RhoA
- the PH (pleckstrin-homology) domain is involved in
- microtubule binding & targeting to tight junctions
- contains 1 DH (DBL-homology) domain
- contains 1 PH domain
- contains 1 phorbol-ester/DAG-type Zn+2 finger
Compartment
- cytoplasm
- cell junction, tight junction
- Golgi
- cytoskeleton, spindle
- cell projection, ruffle membrane
- localizes to the tips of cortical microtubules of the mitotic spindle during cell division, & is released upon microtubule depolymerization
- recruited into membrane ruffles induced by S flexneri at tight junctions of polarized epithelial cells
Alternative splicing
named isoforms=3
More general terms
References
- ↑ UniProt http://www.uniprot.org/uniprot/Q92974.html
- ↑ Atlas of Genetics & Cytogenetics in Oncology & Haematology http://atlasgeneticsoncology.org/genes/ARHGEF2ID43150ch1q22.html
- ↑ Wikipedia; Note: ARHGEF2 entry http://en.wikipedia.org/wiki/ARHGEF2