What is GEF-H1?
GEF-H1 is a microtubule-associated Rho GEF23 that couples microtubule dynamics to cell contractility. 24. A previous study established that its release upon microtubule depolymerization stimulates nucleotide exchange by RhoA. 24. In contrast, re-association of GEF-H1 with microtubules inhibits its enzymatic activity.
What kind of protein is GEF-H1?
GEF-H1 encodes a 100-kDa protein containing the conserved structural array of a Dbl homology domain in tandem with a pleckstrin homology domain and is most closely related to the lfc oncogene, but additionally it contains a unique coiled-coil domain at the carboxyl terminus.
What activates GEFs?
Guanine nucleotide exchange factors (GEFs) are proteins or protein domains that activate monomeric GTPases by stimulating the release of guanosine diphosphate (GDP) to allow binding of guanosine triphosphate (GTP).
What is GEF G protein?
Guanine nucleotide exchange factors (GEFs) are a family of proteins that facilitate the release of GDP from the small G-protein, which allows the binding of GTP, which is at much higher cytoplasmic concentrations, thereby promoting activation of the GTPase.
What is GEF and GAP?
GEFs and GAPs are multidomain proteins that are regulated by extracellular signals and localized cues that control cellular events in time and space. Recent evidence suggests that these proteins may be potential therapeutic targets for developing drugs to treat various diseases, including cancer.
What is GAP vs GEF?
In general, GEFs turn on signaling by catalyzing the exchange from G-protein-bound GDP to GTP, whereas GAPs terminate signaling by inducing GTP hydrolysis. GEFs and GAPs are multidomain proteins that are regulated by extracellular signals and localized cues that control cellular events in time and space.
What does GAP and GEF do?
Guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs) regulate the activity of small guanine nucleotide-binding (G) proteins to control cellular functions.
What is GEF to Ras?
These GEFs contain a CDC25-HD, which acts specifically on Ral, and in addition a Ras-association (RA) domain, which interacts with the GTP-bound states of Ras and Rap. Ras induces the translocation of RalGDS to the plasma membrane and thereby increases RalGTP levels (Urano et al., 1996).
What is ran GEF?
Ran (RAs-related Nuclear protein) also known as GTP-binding nuclear protein Ran is a protein that in humans is encoded by the RAN gene. Ran is a small 25 kDa protein that is involved in transport into and out of the cell nucleus during interphase and also involved in mitosis.
What does the G in G protein stand for?
guanine nucleotide-binding proteins
G proteins, also known as guanine nucleotide-binding proteins, are a family of proteins that act as molecular switches inside cells, and are involved in transmitting signals from a variety of stimuli outside a cell to its interior.
Why is there no stimulation of GEF-H1 in the assay?
The lack of stimulation of GEF-H1 activity, however, might be due to the limitations of the assay used. The amount of precipitated GEF-H1 used in the assay is hard to standardize, and GEF-H1 might lose its activated state during the process of precipitation and elution from the beads.
What is the function of GEF H1 in epithelial cells?
In tubular epithelial cells, GEF-H1 is also stimulated by tumor necrosis factor α (TNFα) and mediates RhoA activation and increased paracellular permeability (19). GEF-H1 may thus play a pathological role in the disruption of junctional complexes and epithelial cell barrier.
What is the role of GEF-H1 in permeability?
Previous studies have shown an important role of GEF-H1 in the regulation of paracellular permeability in epithelial and endothelial cells (14, 17). GEF-H1 was also shown to mediate RhoA and Rho kinase activation upon Ca2+removal, leading to the disassembly of the apical junctional complexes (18).
Is GEF-H1 a microtubule protein?
GEF-H1 is also known to be a microtubule-associated protein (15). It has been shown that GEF-H1 bound to the microtubule is inactive and that microtubule depolymerization liberates GEF-H1, allowing it to activate RhoA (39, 40). Moreover, activation of GEF-H1 by mechanical stimuli was found to be mediated by the microtubules (16, 17, 39).