Rho Gtpase
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Rho Gtpase
The Rho family of GTPases is a family of small (~21 kDa) signaling G proteins, and is a subfamily of the Ras superfamily. The members of the Rho GTPase family have been shown to regulate many aspects of intracellular actin dynamics, and are found in all eukaryotic kingdoms, including yeasts and some plants. Three members of the family have been studied in detail: Cdc42, Rac1, and RhoA. All G proteins are "molecular switches", and Rho proteins play a role in organelle development, cytoskeletal dynamics, cell movement, and other common cellular functions. History Identification of the Rho family of GTPases began in the mid-1980s. The first identified Rho member was RhoA, isolated serendipitously in 1985 from a low stringency cDNA screening. Rac1 and Rac2 were identified next, in 1989 followed by Cdc42 in 1990. Eight additional mammalian Rho members were identified from biological screenings until the late 1990s, a turning point in biology where availability of complete genome se ...
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G Protein
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. Their activity is regulated by factors that control their ability to bind to and hydrolyze guanosine triphosphate (GTP) to guanosine diphosphate (GDP). When they are bound to GTP, they are 'on', and, when they are bound to GDP, they are 'off'. G proteins belong to the larger group of enzymes called GTPases. There are two classes of G proteins. The first function as monomeric small GTPases (small G-proteins), while the second function as heterotrimeric G protein complexes. The latter class of complexes is made up of '' alpha'' (α), ''beta'' (β) and ''gamma'' (γ) subunits. In addition, the beta and gamma subunits can form a stable dimeric complex referred to as the beta-gamma complex . Heterotrimeric G proteins located within the cell are activ ...
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Filopodia
Filopodia (singular filopodium) are slender cytoplasmic projections that extend beyond the leading edge of lamellipodia in migrating cells. Within the lamellipodium, actin ribs are known as ''microspikes'', and when they extend beyond the lamellipodia, they're known as filopodia. They contain microfilaments (also called actin filaments) cross-linked into bundles by actin-bundling proteins, such as fascin and fimbrin. Filopodia form focal adhesions with the substratum, linking them to the cell surface. Many types of migrating cells display filopodia, which are thought to be involved in both sensation of chemotropic cues, and resulting changes in directed locomotion. Activation of the Rho family of GTPases, particularly cdc42 and their downstream intermediates, results in the polymerization of actin fibers by Ena/Vasp homology proteins. Growth factors bind to receptor tyrosine kinases resulting in the polymerization of actin filaments, which, when cross-linked, make up the sup ...
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RHOBTB2
Rho-related BTB domain-containing protein 2 is a protein that in humans is encoded by the ''RHOBTB2'' gene. RHOBTB2 is a member of the evolutionarily-conserved RhoBTB subfamily of Rho GTPases. For background information on RhoBTBs, see RHOBTB1 (MIM 607351). upplied by OMIMref name="entrez"/> Clinical significance Mutations affecting ''RHOBTB2'' can cause epilepsy, learning difficulties and movement disorders. ''RHOBTB2''-related disorders are autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ..., meaning only one of the two copies of the gene needs to be mutated to cause disease. The mutations usually occur ''de novo'' – that is, as a new mutation occurring in the affected individual rather than having been inherited. References Further reading

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RHOBTB1
Rho-related BTB domain-containing protein 1 is a protein that in humans is encoded by the ''RHOBTB1'' gene. The protein encoded by this gene belongs to the Rho family of the Ras superfamily The Ras superfamily, derived from "Rat sarcoma virus", is a protein superfamily of small GTPases. Members of the superfamily are divided into families and subfamilies based on their structure, sequence and function. The five main families are Ras ... of small GTPases. It contains a GTPase domain, a proline-rich region, a tandem of 2 BTB (broad complex, tramtrack, and bric-a-brac) domains, and a conserved C-terminal region. The protein plays a role in small GTPase-mediated signal transduction and the organization of the actin filament system. Alternate transcriptional splice variants have been characterized. References Further reading

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RhoBTB
The RhoBTB family is a subgroup of the Rho family of small GTPases. They are a highly divergent class and are all characterized by an N-terminal Rho-related domain followed by at least one C-terminal BTB domain. Discovery The RhoBTB family of molecules was unknowingly discovered in 1993 by analyzing the Dictyostelium genome looking for members of the Ras superfamily of GTPases. The authors began by doing Southern blots looking for cDNAs that cross-hybridize with a very conservative probe from hRas. They identified 19 new genes that belonged to the Ras superfamily and sequenced approximately 600 nucleotides from the start of the transcript. If they were looking for a normal Ras-like GTPase, this would have been sufficient. One of their clones, they called RacA, was more divergent than most of the others and the transcript didn’t terminate in a stop codon like the rest. The authors, however, didn’t comment on this and RhoBTB went undiscovered for another eight years. ...
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RhoG
RhoG (Ras homology Growth-related) (or ARGH) is a small (~21 kDa) monomeric GTP-binding protein (G protein), and is an important component of many intracellular signalling pathways. It is a member of the Rac subfamily of the Rho family of small G proteins and is encoded by the gene RHOG. Discovery RhoG was first identified as a coding sequence upregulated in hamster lung fibroblasts upon stimulation with serum. Expression of RhoG in mammals is widespread and studies of its function have been carried out in fibroblasts, leukocytes, neuronal cells, endothelial cells and HeLa cells. RhoG belongs to the Rac subgroup and emerged as a consequence of retroposition in early vertebrates. RhoG shares a subset of common binding partners with Rac, Cdc42 and RhoU/V members but a major specificity is its inability to bind to CRIB domain proteins such as PAKs. Function Like most small G proteins RhoG is involved in a diverse set of cellular signalling mechanisms. In mammalian cells these inc ...
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Rac (GTPase)
Rac is a subfamily of the Rho family of GTPases, small (~21 kDa) signaling G proteins (more specifically a GTPase). Just as other G proteins, Rac acts as a molecular switch, remaining inactive while bound to GDP and activated once GEFs remove GDP, permitting GTP to bind. When bound to GTP, Rac is activated. In its activated state, Rac participates in the regulation of cell movement, through its involvement in structural changes to the actin Cytoskeleton. By changing the cytoskeletal dynamics within the cell, Rac-GTPases are able to facilitate the recruitment of neutrophils to the infected tissues, and to regulate degranulation of azurophil and integrin-dependent phagocytosis. Activated Rac also regulates the effector functions of the target proteins involved in downstream signaling. As an essential subunit of NOX2 (NADPH oxidase enzyme complex), Rac is required for ROS (reactive oxygen species) production involved in the formation of NETs (neutrophil extracellular traps, thus, f ...
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Chp (GTPase)
RhoV (or Chp or Wrch2) is a small (~21 kDa) signaling G protein (more specifically a GTPase), and is a member of the Rho family of GTPases. Chp was identified in 1998 as a GTPase interacting with the p21 activated kinase PAK2. RhoV/Chp delineates with RhoU/Wrch a Rho subclass related to Rac and Cdc42, which emerged in early multicellular organisms during evolution. RhoV/Chp depends on palmitoylation rather than prenylation for association with plasma and intracellular membranes. In Xenopus embryos, RhoV is encoded by a canonical Wnt response gene and is induced in the developing neural crest at specification. RhoV activity cooperates with the Snai1 (Snail) transcription factor for the subsequent induction of the pro-invasive transcription factors Snai2 (Slug), Sox9 or Twist. ''Further reading: Rho family of GTPases The Rho family of GTPases is a family of small (~21 kDa) signaling G proteins, and is a subfamily of the Ras superfamily. The members of the Rho GTPase family have ...
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Wrch1
RhoU (or Wrch1 or Chp2) is a small (~21 kDa) signaling G protein (more specifically a GTPase), and is a member of the Rho family of GTPases. Wrch1 was identified in 2001 as encoded by a non-canonical Wnt induced gene. RhoU/Wrch delineates with RhoV/Chp a Rho subclass related to Rac and Cdc42, which emerged in early multicellular organisms during evolution. Model organisms Model organisms have been used in the study of RhoU function. A conditional knockout mouse line, called ''Rhoutm1a(KOMP)Wtsi'' was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty three tests were carried out on mutant In biology, and especially in genetics, a mutant is an organism or a new genetic character ...
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RHOJ
Rho-related GTP-binding protein RhoJ is a protein that in humans is encoded by the ''RHOJ'' gene. ARHJ belongs to the Rho family of small GTP-binding proteins. Rho proteins regulate the dynamic assembly of cytoskeletal components for several physiologic processes, such as cell proliferation and motility and the establishment of cell polarity. They are also involved in pathophysiologic process, such as cell transformation and metastasis Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, .... upplied by OMIMref name="entrez" /> References Further reading

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