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human brain malformation is recapitulated in Arhgef2 mutant mice and identify an aberrant migration of distinct components of the precerebellar system as a pathomechanism underlying the midbrain-hindbrain phenotype. Our results highlight the crucial function of ARHGEF2 in human brain development and identify a mutation in ARHGEF2 as novel cause of a neurodevelopmental disorder.
These results identify GEF-H1 as a component of the shear stress response machinery in neutrophils required for a fully competent immune response to bacterial infection.
Study describes a new mode of GEF-H1 activation in response to G-protein-coupled receptor (GPCR (show TAS1R3 Proteins)) ligands that is independent of microtubule depolymerization.
Data show that the activation of the microtubule-associated guanine nucleotide exchange factor (show ARHGEF12 Proteins) GEF-H1, encoded by Arhgef2, is essential for sensing of foreign RNA by RIG-I (show DDX58 Proteins)-like receptors.
Pak2 (show PAK2 Proteins), but not Pak1 (show PAK1 Proteins), negatively regulates RhoA (show RHOA Proteins) via phosphorylation of the guanine nucleotide exchange factor (show ARHGEF12 Proteins) GEF-H1 at an inhibitory site, leading to increased GEF-H1 microtubule binding and loss of RhoA (show RHOA Proteins) stimulation
It was shown that the guanine exchange factors GEF-H1 and ECT2 (show ECT2 Proteins) must be downregulated for megakaryote polyploidization. The first (2N-4N) endomitotic cycle requires GEF-H1 downregulation, whereas subsequent cycles (>4N) require ECT2 (show ECT2 Proteins) downregulation.
CAPN6 (show CAPN6 Proteins) acts as a regulator of Rac1 and cell motility through interaction with GEF-H1.
LARG is activated by the Src family tyrosine kinase Fyn, whereas GEF-H1 catalytic activity is enhanced by ERK downstream of a signalling cascade that includes FAK and Ras
p114-RhoGEF (show ARHGEF18 Proteins) and Lfc are critically involved in Wnt-3a (show WNT3A Proteins)- and Dvl (show DVL1 Proteins)-induced RhoA (show RHOA Proteins) activation and neurite retraction in N1E-115 cells.
Depletion of GEF-H1 in the murine two-hit model of VILI attenuated vascular leak induced by lung ventilation at high tidal volume and thrombin (show F2 Proteins)-derived peptide TRAP6.
depletion induces phosphorylation of the microtubule-associated GEF-H1 on Ser886, and thereby promotes RhoA activity and actin stress fiber assembly.
Overexpression of miR (show MLXIP Proteins)-194 downregulates the GEF-H1/RhoA (show RHOA Proteins) pathway, inhibits melanoma cancer cell proliferation and metastasis. Furthermore, miR (show MLXIP Proteins)-194 expression is negatively associated with tumor-node-metastasis (TNM (show ODZ1 Proteins)) stages
data suggest that the induction of SGK1 (show SGK1 Proteins) through treatment with dexamethasone alters MT dynamics to increase Sec5-GEF-H1 interactions, which promote GEF-H1 targeting to adhesion sites.
this study reports the crystal structure of human GEF-H1 PH domain to 2.45 A resolution.
By stimulating cofilin (show CFL1 Proteins)/PP2A (show PPP2R4 Proteins)-mediated dephosphorylation of the guanine nucleotide exchange factor (show RASGRF1 Proteins) GEF-H1.
regulation of c-Src trafficking requires both microtubules and actin polymerization, and GEF-H1 coordinates c-Src trafficking, acting as a molecular switch between these two mechanisms
Results supported that miR-512-3p could inhibit tumor cell adhesion, migration, and invasion by regulating the RAC1 activity via DOCK3 in NSCLC A549 and H1299 cell lines.
TGF-beta (show TGFB1 Proteins) regulates LARG (show ARHGEF12 Proteins) and GEF-H1 during epithelial-mesenchymal transition to affect stiffening response to force and cell invasion.
Our findings underscore a potent oncogenic role for GEF-H1 in promoting the metastatic potentials of hepatocellular carcinoma, possibly through activation of RhoA (show RHOA Proteins) signalling.
Data indicate that TNF-alpha (show TNF Proteins) stimulates Rac (show AKT1 Proteins), ADAM17/TACE (show ADAM17 Proteins), and RhoA (show RHOA Proteins) through the guanine nucleotide exchange factor (show ARHGEF12 Proteins) (GEF)-H1.
Data indicate that GEF-H1 is a target and functional effector of TGF-beta (show TGFB1 Proteins) by orchestrating Rho signaling to regulate gene expression and cell migration.
ERK/GEF-H1/Rho/ROK/pMLC pathway could be a central mechanism whereby electrogenic transmembrane transport processes control myosin phosphorylation and regulate paracellular transport in the tubular epithelium.
the ERK (show MAPK1 Proteins)/GEF-H1/Rho/Rho kinase (show ROCK1 Proteins)/phospho-MLC pathway is the mechanism mediating TNF-alpha (show TNF Proteins)-induced elevation of tubular epithelial permeability, which in turn might contribute to kidney injury
Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli that work through G protein coupled receptors. The encoded protein may form complex with G proteins and stimulate rho-dependent signals. Alternatively spliced transcript variants encoding different isoforms have been identified.
Rho/Rac guanine nucleotide exchange factor (GEF) 2
, guanine nucleotide exchange factor LFC
, Rho/Rac guanine nucleotide exchange factor 2
, rho guanine nucleotide exchange factor 2-like
, LBC'S first cousin
, guanine nucleotide exchange factor H1
, lymphoid blast crisis-like 1
, oncogene LFC
, rho guanine nucleotide exchange factor 2
, microtubule-regulated Rho-GEF
, proliferating cell nucleolar antigen p40
, Guanine nucleotide exchange factor H1
, rho/rac guanine nucleotide exchange factor 2
, tight junction-associated guanine nucleotide exchange factor