• Transforming protein RhoA, also known as Ras homolog family member A (RhoA), is a small GTPase protein in the Rho family of GTPases that in humans is encoded by the RHOA gene. (wikipedia.org)
  • The C-terminal of RhoA is modified via prenylation, anchoring the GTPase into membranes, which is essential for its role in cell growth and cytoskeleton organization. (wikipedia.org)
  • Rho GTPases represent a family of small GTP-binding proteins involved in cell cytoskeleton organization, migration, transcription, and proliferation. (biomedcentral.com)
  • Mainly associated with cytoskeleton organization, in active state binds to a variety of effector proteins to regulate cellular responses such as cytoskeletal dynamics, cell migration and cell cycle. (cusabio.com)
  • RhoA directly stimulates actin polymerization through activation of diaphanous-related formins, thereby structurally changing the actin monomers to filaments. (wikipedia.org)
  • the actin filaments represent the retrograde flow and the blue arrows indicate its characteristic centripetal flow. (mechanobio.info)
  • How do actin filaments form higher-order assemblies that produce and respond to force? (mechanobio.info)
  • Cells exert traction forces on the ECM and generate tension at focal adhesions through actin stress fibers , which are higher-order structures in the cytoplasm that consist of parallel contractile bundles of actin and myosin filaments. (mechanobio.info)
  • Cell tension is generated along the actin filaments by the movement of myosin II motor proteins along the filaments (see contractile bundles). (mechanobio.info)
  • Similar to other GTPases, RhoA presents a Rho insert in its primary sequence in the GTPase domain. (wikipedia.org)
  • these states alternate between the active and inactive states via the exchange of GDP to GTP (conducted simultaneously via guanine nucleotide exchange factors and GTPase activating factor). (wikipedia.org)
  • A common theme of these processes is a dynamic reorganization of actin cytoskeleton which has now emerged as a major switch control mainly carried out by Rho and Rac GTPase subfamilies, playing an acknowledged role in adaptation of cell motility to the microenvironment. (biomedcentral.com)
  • A structural feature that distinguishes the Rho proteins from other small GTPases is the so-called Rho insert domain located between a β strand and an α helix within the small GTPase domain [ 1 - 3 ]. (biomedcentral.com)
  • Typically Rho proteins are 190-250 residues long and consist only of the GTPase domain and short terminal C-terminal extensions. (biomedcentral.com)
  • Within their GTPase domains, they share approximately 30% amino acid identity with the Ras proteins and 40-95% identity within the family. (biomedcentral.com)
  • Rho GTPase effectors are a large group of proteins and include actin nucleation promoting molecules, adaptors, as well as kinases. (biomedcentral.com)
  • ARHGAP21 interacts with RhoA-GTP, and acts as a GAP to increase RhoA GTPase activity. (uth.edu)
  • Small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state. (cusabio.com)
  • Signal transduction pathways regulated via RhoA link plasma membrane receptors to focal adhesion formation and the subsequent activation of relevant actin stress fibers. (wikipedia.org)
  • The best-characterized molecules are Rho, which controls the stress fibers and focal adhesion formation, and Rac and Cdc42, which regulate membrane ruffling, and filopodium formation, respectively. (biomedcentral.com)
  • Acts as an allosteric activator of guanine nucleotide exchange factor ECT2 by binding in its activated GTP-bound form to the PH domain of ECT2 which stimulates the release of PH inhibition and promotes the binding of substrate RHOA to the ECT2 catalytic center. (cusabio.com)
  • RhoA is sequestered by dissociation inhibitors (RhoGDIs) which remove the protein from the membrane while preventing its further interaction with other downstream effectors. (wikipedia.org)
  • These structural arrangements provide interaction sites that can interact with effectors and guanine factors in order to stabilize and signal the hydrolysis of GTP. (wikipedia.org)
  • In turn, GTP-bound active GTPases can interact with a plethora of different effectors which mediate the different cellular functions of this family of proteins. (biomedcentral.com)
  • Activation levels of RhoA and associated GEFs are measured using RhoA and GEF pull down assays that uses Rhotekin and mutant RhoA G17A beads respectively RhoA is primarily involved in these activities: actin organization, myosin contractility, cell cycle maintenance, cellular morphological polarization, cellular development and transcriptional control. (wikipedia.org)
  • The exchange of GDP to GTP and thus the activation of Rho GTPases is catalyzed by guanine nucleotide exchange factors (GEFs), which act downstream of numerous growth factor receptors, integrins, cytokine receptors, and cadherins. (biomedcentral.com)
  • Each myosin motor protein possesses ATPase activity and functions in a cyclical manner that couples ATP binding and hydrolysis to a conformational change in the protein. (mechanobio.info)
  • What is the structure of the myosin motor proteins? (mechanobio.info)
  • The primary protein sequences of members of the Rho family are mostly identical, with the N-terminal containing most of the protein coding for GTP binding and hydrolysis. (wikipedia.org)
  • Key amino acids that are involved in the stabilization and regulation of GTP hydrolysis are conserved in RhoA as Gly14, Thr19, Phe30 and Gln63. (wikipedia.org)
  • Most importantly, RhoA contains two switch regions, Switch I and Switch II, whose conformational states are modified following the activation or inactivation of the protein. (wikipedia.org)
  • The nature of the bound nucleotide and the ensuing conformational modification of the Switch domains dictates the ability of RhoA to bind or not with partner proteins (see below). (wikipedia.org)
  • RhoA, and the other Rho GTPases, are part of a larger family of related proteins known as the Ras superfamily, a family of proteins involved in the regulation and timing of cell division. (wikipedia.org)
  • RhoA is one of the oldest Rho GTPases, with homologues present in the genomes since 1.5 billion years. (wikipedia.org)
  • Rho GTPases work as sensitive molecular switches existing either in an inactive, GDP-bound form or an active GTP-bound form. (biomedcentral.com)
  • In turn, membrane-bound APC allows the localization of the MACF1 to the cell membrane, which is required for microtubule capture and stabilization. (cusabio.com)
  • Among them, ROCK1 (Rho-associated, coiled-coil containing protein kinase 1) and DIAPH1 (Diaphanous Homologue 1, a.k.a. hDia1, homologue to mDia1 in mouse, diaphanous in Drosophila) are the best described. (wikipedia.org)
  • They are endowed with GTP hydrolytic activity, mainly involved in cytoskeleton rearrangements and cell motility, but also involved in cell proliferation, transformation and differentiation [ 2 ]. (biomedcentral.com)
  • Both of these switches have characteristic folding, correspond to specific regions on the RhoA coil and are uniformly stabilized via hydrogen bonds. (wikipedia.org)
  • All members contain the sequence motifs characteristic of all GTP-binding proteins, bind to GDP and GTP with high affinity. (biomedcentral.com)
  • ROCK kinases induce actomyosin-based contractility and phosphorylate TAU and MAP2 involved in regulating myosins and other actin-binding proteins in order to assist in cell migration and detachment. (wikipedia.org)
  • As a consequence, RhoA is somehow involved in many cellular processes which emerged throughout evolution. (wikipedia.org)
  • The cytoskeleton is a highly dynamic network of filamentous proteins that enables the active transport of cellular cargo, transduces force, and when assembled into higher-order structures, forms the basis for motile cellular structures that promote cell movement. (mechanobio.info)
  • RhoA specifically is regarded as a prominent regulatory factor in other functions such as the regulation of cytoskeletal dynamics, transcription, cell cycle progression and cell transformation. (wikipedia.org)
  • The specific gene that encodes RhoA, RHOA, is located on chromosome 3 and consists of four exons, which has also been linked as a possible risk factor for atherothrombolic stroke. (wikipedia.org)
  • The MEMO1-RHOA-DIAPH1 signaling pathway plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. (cusabio.com)
  • Note: The complete sequence including tag sequence, target protein sequence and linker sequence could be provided upon request. (cusabio.com)
  • Stress fibers are linked at their ends to the ECM through focal adhesion complexes. (mechanobio.info)
  • Required for the apical junction formation of keratinocyte cell-cell adhesion. (cusabio.com)
  • They are small (21-25 kDa) molecules that share structural homology and become activated only when bound to GTP. (biomedcentral.com)
  • In addition, RhoA is believed to act primarily at the rear (uropod) of migrating cells to promote detachment, similar to the attachment and detachment process found in the focal adhesion mechanism. (wikipedia.org)