• Growth inhibitory proteins in the central nervous system (CNS) block axon growth and regeneration by signaling to Rho, an intracellular GTPase. (silverchair.com)
  • These findings suggest that changes in Rho GTPase activity, linked to AD, are more complex than previously thought, underscoring the need for further investigation into signaling pathways governing the onset of dendritic spine loss. (saneurociencias.org.ar)
  • Rho GTPase activation through stimulation with specific L-selectin ligands has been proposed to modulate tight junctional dynamics. (tmu.edu.tw)
  • However, little is known regarding the role of Ca +2 dynamics in Sertoli cell and how Ca +2 relays L-selectin signals to modulate Rho GTPase activity in Sertoli cells, thus prompting us to investigate the Ca +2 flux induced by L-selectin ligand in ASC-17D cells. (tmu.edu.tw)
  • Cytoplasmic Ca 2+ elevation and changes in Rho GTPase activity are both known to mediate axon guidance by extracellular factors, but the causal relationship between these two events has been unclear. (jneurosci.org)
  • Furthermore, Ca 2+ -induced GTPase activity correlated with activation of protein kinase C and required a basal activity of Ca 2+ /calmodulin-dependent protein kinase II. (jneurosci.org)
  • The small GTPase Rho can regulate several aspects of cellular function, predominantly through its downstream effector Rho-kinase. (uni-muenchen.de)
  • 2006) Combined integrin activation and intracellular cAMP cause Rho GTPase dependent growth cone collapse on laminin-1. (assumption.edu)
  • Transforming activity of the Rho family GTPase, Wrch-1, a Wnt-regulated Cdc42 homolog, is dependent on a novel carboxyl-terminal palmitoylation motif. (xenbase.org)
  • Biochemical data have established the role of the conserved DH domain in Rho GTPase interaction and activation, and the role of the tandem PH domain in intracellular targeting and/or regulation of DH domain function. (embl-heidelberg.de)
  • CR1 and CR3, together with a part of alpha-6 and the DH/PH junction site, constitute the Rho GTPase interacting pocket. (embl-heidelberg.de)
  • Using single molecule Total Internal Reflection Fluorescence (TIRF) Microscopy, we determined the mechanism controlling membrane localization of PI3Kβ, prioritization of signaling inputs, and lipid kinase activation. (elifesciences.org)
  • Like Rho-kinase activation, it was also found that LIMK-1 activation was independent and upstream of integrin IIbβ3 activation. (uni-muenchen.de)
  • Nuclear efflux of heterogeneous nuclear ribonucleoprotein C1/C2 in apoptotic cells: a novel nuclear export dependent on Rho-associated kinase activation. (ntu.edu.tw)
  • Here we applied this system to an intracellular Rho-associated coiled-coil kinase (ROCK) signal, which is activated abnormally in cardiovascular diseases. (elsevierpure.com)
  • Using ryanodine to directly trigger intracellular [Ca 2+ ] i elevation, we showed in the present work that Rho GTPases can function downstream of Ca 2+ signals to mediate growth cone turning, although GTPases activity can also affect slightly the Ca 2+ signal. (jneurosci.org)
  • Chaves-Olarte E , Guzmán-Verri C , Méresse S , Desjardins M , Pizarro-Cerdá J , Badilla J , Activation of Rho and Rab GTPases dissociate Brucella abortus internalization from intracellular trafficking. (cdc.gov)
  • Their activity is regulated by phosphorylation of a threonine residue within the activation loop by intracellular signaling kinases such as P21-ACTIVATED KINASES and by RHO KINASE. (bvsalud.org)
  • The use of C3 transferase to inactivate Rho in primary neurons plated on various types of inhibitory proteins and dominant-negative Rho-expressing PC-12 cells provides direct evidence that the inactivation of Rho results in neurite outgrowth on inhibitory substrates. (silverchair.com)
  • Together, we conclude that the activation of L-selectin induces Ca +2 influx through the L-type VOCC, which up-regulates Rho and Rac1 proteins, in ASC-17D cells. (tmu.edu.tw)
  • The morphological and functional changes of platelets require a drastic remodeling of the actin cytoskeleton regulated by numerous actin-binding proteins and signaling molecules such as the family of Rho-GTPases. (uni-muenchen.de)
  • Rho proteins promote reorganization of the actin cytoskeleton and regulate cell shape, attachment, and motility. (cancerindex.org)
  • This protein is a member of the Dbl family of guanine nucleotide exchange factors (GEF) for the Rho family of GTP binding proteins. (avivasysbio.com)
  • Coexpression and binding of these partners initiates profound morphological changes, cytoskeletal rearrangements and the JNK/SAPK signaling cascade, leading to increased levels of viral transcription and replication.The protein encoded by this proto-oncogene is a member of the Dbl family of guanine nucleotide exchange factors (GEF) for the Rho family of GTP binding proteins. (avivasysbio.com)
  • Like all members of the Ras superfamily, the Rho proteins cycle between active GTP-bound and inactive GDP-bound conformational states. (embl-heidelberg.de)
  • Activation of Rho proteins through release of bound GDP and subsequent binding of GTP, is catalysed by guanine nucleotide exchange factors (GEFs) in the Dbl family. (embl-heidelberg.de)
  • The proteins encoded by members of the Dbl family share a common domain, presented in this entry, of about 200 residues (designated the Dbl homology or DH domain) that has been shown to encode a GEF activity specific for a number of Rho family members. (embl-heidelberg.de)
  • It does not share significant sequence homology with other subtypes of small G-protein GEF motifs such as the Cdc25 domain and the Sec7 domain, which specifically interact with Ras and ARF family small GTPases, respectively, nor with other Rho protein interactive motifs, indicating that the Dbl family proteins are evolutionarily unique. (embl-heidelberg.de)
  • The Rho family of GTP-binding proteins has been implicated in the regulation of various cellular functions including actin cytoskeleton-dependent morphological change. (embl-heidelberg.de)
  • The guanine nucleotide exchange factor (GEF) Dbl targets Rho family proteins thereby stimulating their GDP/GTP exchange, and thus is believed to be involved in receptor-mediated regulation of the proteins. (embl-heidelberg.de)
  • Inhibition of HMG-CoA reductase by statin in effect prevents the synthesis of mevalonic acid, a precursor of nonsteroidal isoprenoids, lipid attachment molecules for small G proteins, such as Ras, Rho, and Rac. (cdc.gov)
  • Thus, statins may inhibit the synthesis of isoprenoids and thereby suppress the activation of small G proteins (7). (cdc.gov)
  • Previous studies have implicated RhoA in platelet activation. (nih.gov)
  • Rhosin/G04 contains a pair of enantiomers, and S-G04 is significantly more potent than R-G04 in inhibiting RhoA activation and platelet aggregation. (nih.gov)
  • It is not known how CNS trauma affects the expression and activation of RhoA. (silverchair.com)
  • Using these tools, we aimed to gather new and detailed evidence on the activation dynamics of Rho GTPases-RhoA, Rac1, and Cdc42-during early and late exposure to pathogenic forms of β-amyloid 1-42 in cell lines and neuronal cultures. (saneurociencias.org.ar)
  • Plexin-B1 has recently been shown to mediate activation of RhoA through a stable interaction with the Rho guanine nucleotide exchange factors PDZ-RhoGEF and LARG. (rupress.org)
  • A dominant-negative form of ErbB-2 blocks Sema4D-induced RhoA activation as well as axonal growth cone collapse in primary hippocampal neurons. (rupress.org)
  • Our data indicate that ErbB-2 is an important component of the plexin-B receptor system and that ErbB-2-mediated phosphorylation of plexin-B1 is critically involved in Sema4D-induced RhoA activation, which underlies cellular phenomena downstream of plexin-B1, including axonal growth cone collapse. (rupress.org)
  • This G-LISA™ Rho activation assay measures the levels of GTP-loaded RhoA in cells. (cytoskeleton.com)
  • For a kit to measure RhoA activation with colorimetric detection, see Cat. (cytoskeleton.com)
  • The aim was to determine the degree of association between Rho-kinase cascade activation in circulating leukocytes with cardiac and aortic Rho-kinase pathway activation in a model of hypertension and to analyze it with a cause-effect perspective. (portlandpress.com)
  • Moreover, the Nogo-A-Δ20 domain promotes neuroblast migration toward the OB through activation of the Rho/ROCK (Rho-associated, coiled-coil containing protein kinase) pathway, without the participation of NgR1. (jneurosci.org)
  • Rho-kinase regulates a second pathway that involves activation of LIM-kinases (LIMKs) and subsequent phosphorylation and inactivation of cofilin, an actin dynamizing protein. (uni-muenchen.de)
  • The signaling pathway Rho-kinase/LIMKs/cofilin phosphorylation during platelet activation and the question, how the phosphorylation of cofilin affects the actin dynamics underlying platelet activation, has not previously been studied. (uni-muenchen.de)
  • Inhibition of the Rho-kinase/LIMK-1 pathway unmasked cofilin dephosphorylation suggesting that during shape change the simultaneous activation of a cofilin phosphatase counteracts the effect of LIMK-1 for phosphorylating cofilin. (uni-muenchen.de)
  • Since the kinetics of cofilin phospho-cycle was similar during secretion and platelet aggregation in LPA- and thrombin-stimulated cells, I propose a general two-step regulatory process for cofilin phospho-cycle underlying primarily secretion, and subsequently platelet aggregation: dephosphorylation by a cofilin phosphatase and then rephosphorylation by the Rho-kinase/LIMK-1 pathway. (uni-muenchen.de)
  • Bioinformatic analysis of the gene expression data identified significant enrichment of several diseases/biological function categories (for example, cancer, leukocyte migration, inflammatory response, mitosis, and movement of phagocytes) and canonical pathways (for example, kinetochore metaphase signaling pathway, granulocyte and agranulocyte adhesion and diapedesis, acute phase response, and LXR/RXR activation). (cdc.gov)
  • Furthermore, we found that the Ca 2+ effector enzyme protein kinase C (PKC) is essential for the Ca 2+ -dependent regulation of Rho GTPases during the transduction of guidance signals. (jneurosci.org)
  • Rho-kinase inhibition reduced significantly blood pressure, cardiac hypertrophy, myocardial collagen and macrophage infiltration, but not aortic wall hypertrophy. (portlandpress.com)
  • Therefore, understanding the molecular mechanisms of platelet activation and identifying novel techniques for platelet inhibition remain critically important. (spandidos-publications.com)
  • The mild rise in HDL-C levels from these drugs may be related to inhibition of rho-signaling pathways with activation of peroxisome proliferator-activated receptor (PPAR)-alpha. (medscape.com)
  • One of the well established Rho-kinase-mediated signaling pathways is the phosphorylation of myosin light chain (MLC) and its counteracting MLC phosphatase. (uni-muenchen.de)
  • These findings give a comprehensive view of the evolutionary canvas of the Rho family and provide guides for future structure and evolution studies of other components of Rho signaling pathways, in particular regulators of the RhoGEF family. (xenbase.org)
  • Yen ML, Su JL, Chien CL , Tseng KW, Yang CY, Chen WF, Chang CC, and Kuo ML. Diosgenin induces HIF-1 activation and angiogenesis through estrogen receptor-related PI3K/Akt and p38 MAPK pathways in osteoblasts. (ntu.edu.tw)
  • The mechanisms of chronic kidney disease progression are not well defined, but may include activation of numerous vasoactive and inflammatory pathways. (medscape.com)
  • To mimic activation of Gα12 pathways, constitutively active Gα12 (QL) was conditionally expressed in podocytes using Nphs2-Cre and LacZ/floxed QLα12 transgenic mice. (medscape.com)
  • Targeting activated Gα subunits to specific cells in vivo permits identification of downstream effector pathways independent of receptor activation, and thus permits insight into disease mechanisms otherwise impossible to study in vivo . (medscape.com)
  • However, the mechanisms underlying receptor-dependent regulation of Rho family members remain incompletely understood. (embl-heidelberg.de)
  • We then demonstrated the up-regulation of Rho and Rac1 in ASC-17D cells following the administration of L-selectin ligand, and the pre-treatment with nifedipine, but not mibefradil, prior to L-selectin ligand-binding abolished the activation of both Rho and Rac1. (tmu.edu.tw)
  • One of the important aspects of platelet activation is to understand the dynamic regulation and rearrangement of the cytoskeleton after stimulation. (uni-muenchen.de)
  • Originally demonstrated to control the dynamics of the F- actin cytoskeleton , Rho GTPases have been implicated in many basic cellular processes that influence cell proliferation, differentiation, motility, adhesion, survival, or secretion. (xenbase.org)
  • Cdc42 G-LISA™ Activation Assay, colorimetric format (Cat. (cytoskeleton.com)
  • Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. (embl-heidelberg.de)
  • The Rho family GTPases Rho, Rac and CDC42 regulate a diverse array of cellular processes. (embl-heidelberg.de)
  • The Rho family of small GTPases may serve as "molecular switches" to regulate the cytoskeletal rearrangements involved in many forms of cell motility ( Etienne-Manneville and Hall, 2002 ). (jneurosci.org)
  • The class 1A phosphoinositide 3-kinase (PI3K) beta (PI3Kβ) is functionally unique in the ability to integrate signals derived from receptor tyrosine kinases (RTKs), heterotrimeric guanine nucleotide-binding protein (G-protein)-coupled receptors (GPCRs), and Rho-family GTPases. (elifesciences.org)
  • LIMK-1 can be activated by Rho-kinase as well as by p21-activated kinases (PAKs). (uni-muenchen.de)
  • By another (separable) guanine exchange factor domain domain Sos modulates activity of Rac/Rho GTPases. (novusbio.com)
  • Thus, Rho GTPases may mediate axon guidance by linking upstream Ca 2+ signals triggered by guidance factors to downstream cytoskeletal rearrangements. (jneurosci.org)
  • Hypertensive deoxycorticosterone (DOCA)-salt rats received the Rho-kinase antagonist fasudil (DOCA-Fas, 100 mg/kg/day, 3 weeks). (portlandpress.com)
  • Application of a Rho antagonist (C3-05) reversed Rho activation and reduced the number of TUNEL-labeled cells by ∼50% in both injured mouse and rat, showing a role for activated Rho in cell death after CNS injury. (silverchair.com)
  • This gene encodes a member of the Rho family of small GTPases, which cycle between inactive GDP-bound and active GTP-bound states and function as molecular switches in signal transduction cascades. (cancerindex.org)
  • Our results indicate that blocking overactivation of Rho after SCI protects cells from p75 NTR -dependent apoptosis. (silverchair.com)
  • Tail regression in Ciona intestinalis (Prochordate) involves a Caspase-dependent apoptosis event associated with ERK activation. (xenbase.org)
  • QLα12 LacZ+/Cre+ mice showed no changes in podocyte number, apoptosis, proliferation or Rho/Src activation. (medscape.com)
  • Fasudil decreased significantly Rho-kinase activity in peripheral blood mononucleated cells (PBMC), myocardium and aortic wall to similar levels as in the sham group. (portlandpress.com)
  • Pretreatment with the rho kinase inhibitor, fasudil, was able to prevent brain fluorescein uptake and neuroinflammation. (cdc.gov)
  • It was also found that LGP exhibited marked inhibitory effects on the activation of αIIbβ3 integrin, the secretion of serotonin from granules, and the synthesis of thromboxane A2. (spandidos-publications.com)
  • The activation of Rho-kinase was found to be upstream to secretion and integrin IIbβ3 activation. (uni-muenchen.de)
  • The rapid activation of Rho-kinase during secretion leads to a further increase in F-actin content as compared to shape change. (uni-muenchen.de)
  • It was observed that LPA-stimulated dense granule secretion is mainly regulated by Rho-kinase, whereas secretion induced by thrombin was only in part Rho-kinase-dependent. (uni-muenchen.de)
  • Together, these results show that Rho-kinase regulates the F-actin increase underlying shape change and secretion, but it is not directly involved in aggregation. (uni-muenchen.de)
  • The manuscript describes the synergy among PI3Kβ activators, providing compelling results concerning the mechanism of their activation. (elifesciences.org)
  • Our data establish that the 20 mammalian Rho members are structured into 8 subfamilies, among which Rac is the founder of the whole family. (xenbase.org)
  • However, it has not been biochemically demonstrated that Drosophila myosin motor activity and filament assembly is regulated by RLC phosphorylation or whether the extent of activation is similar to that of mammalian systems. (elifesciences.org)
  • Experiments with p75 NTR -null mutant mice showed that immediate Rho activation after SCI is p75 NTR dependent. (silverchair.com)
  • Our study shows that LIMK-1 activation was mainly Rho-kinase dependent in LPA- and thrombin-stimulated platelets. (uni-muenchen.de)
  • Yang KT, Pan SF, Chien CL , Hsu SM, Tseng YZ, Wang SM, and Wu ML. Mitochondrial Na+ overload is caused by oxidative stress and leads to activation of the caspase 3- dependent apoptotic machinery. (ntu.edu.tw)
  • Herein, we report that genetic activation of Gα12 in podocytes leads to time-dependent increases in proteinuria and glomerulosclerosis. (medscape.com)
  • In most studies examining their activation in AD, biochemical extraction assays, constitutively active or negative dominant mutants are used, which fail to resolve spatio-temporal activation dynamics. (saneurociencias.org.ar)
  • The G-LISA Rho activation assays are ELISA based Rho activation assays with wich you can measure Rho activity in cells in less than 3 h. (cytoskeleton.com)
  • The kit contains sufficient reagents to perform 96 Rho activation assays. (cytoskeleton.com)
  • Since the Rho-GTP affinity wells are supplied as strips and the strips can be broken into smaller pieces, each kit can be used for anywhere from one to multiple assays. (cytoskeleton.com)
  • Rho-kinase activity is determined in circulating leukocytes measuring phosphorylation of its target myosin phosphatase target subunit 1 (MYPT1), but its relationship with Rho-kinase activity in the myocardium and in vasculature in hypertension has not been evaluated. (portlandpress.com)
  • Surprisingly, the activation of LIMK-1 failed to increase cofilin phosphorylation during shape change induced by LPA as well as by thrombin. (uni-muenchen.de)
  • Analysis of Rho mRNA expression patterns in mouse tissues shows that recent subfamilies have tissue -specific and low-level expression that supports their implication only in narrow time windows or in differentiated metabolic functions. (xenbase.org)
  • A significant correlation was found between PBMC Rho-kinase activity and cardiac remodeling, specifically with hypertrophy ( r = 0.51, P ≤0.01), myocardial collagen ( r = 0.40, P ≤0.05) and ED1 immunostaining ( r = 0.48, P ≤0.01). (portlandpress.com)
  • In this model, the activity of Rho GTPases is not merely permissive for growth cone guidance, but directly mediates the guidance signal. (jneurosci.org)
  • mTORC1 activation inhibits autophagy, and it is considered to be a molecular marker of diabetic nephropathy [ 7 , 8 ], as the decrease in podocyte autophagic activity caused by mTORC1 activation plays a vital role in the progression of this disease [ 9 ]. (hindawi.com)
  • In situ Rho-GTP detection revealed that both neurons and glial cells showed Rho activation at SCI lesion sites. (silverchair.com)
  • Taken together, these studies suggest that Gα12 activation promotes glomerular injury without podocyte depletion through a novel mechanism regulating collagen (α)IV expression, and supports the notion that glomerular damage may accrue through persistent GPCR activation in podocytes. (medscape.com)
  • In vertebrates, gene duplications and retrotranspositions increased the size of each chordate Rho subfamily, whereas RhoH , the last subfamily, arose probably by horizontal gene transfer. (xenbase.org)
  • Mutations in the RHO , GNAT1 , or PDE6B gene cause autosomal dominant congenital stationary night blindness. (medlineplus.gov)
  • The RHO gene provides instructions for making a protein called rhodopsin, which is turned on (activated) by light entering the eye. (medlineplus.gov)
  • The α-transducin protein then triggers the activation of a protein called cGMP-PDE, which is made up of multiple parts (subunits) including a subunit produced from the PDE6B gene. (medlineplus.gov)
  • Mutations in the RHO , GNAT1 , or PDE6B gene disrupt the normal signaling that occurs within rod cells. (medlineplus.gov)
  • In many cases this activation is transient, but the mechanisms stopping sustained stimulation remain unexplored 7 . (nature.com)
  • GTPases of the Rho family are molecular switches that play important roles in converting and amplifying external signals into cellular effects. (xenbase.org)
  • TNF-a evokes blood-brain barrier dysfunction through activation of Rho-kinase and neurokinin 1 receptor Immunobiology. (nottingham.ac.uk)
  • Furthermore, the inhibitory effect is reversible, and S-G04 is capable of inhibiting diverse-agonist-stimulated platelet activation. (nih.gov)
  • In conclusion, the data presented here demonstrated that LGP, a natural compound from C. nudiflora Hook, inhibited the development of platelet aggregation and amplification of platelet activation. (spandidos-publications.com)
  • Upon vascular injury, platelets are exposed to the subendothelium, and several agonists, including adenosine diphosphate (ADP) and thrombin, are generated at the injury site, which can stimulate platelet adhesion, activation and aggregation. (spandidos-publications.com)
  • The activation of platelets is a central step during the physiological process of hemostasis and its understanding may lead us to control the pathophysiological process of intra-arterial thrombus formation and vascular occlusion, which can cause acute coronary syndrome and myocardial infarction. (uni-muenchen.de)
  • In this context, Rho GTPases, functioning as molecular switches, are crucial for actin dynamics and dendritic spine structure. (saneurociencias.org.ar)
  • In view of the essential role of both Ca 2+ and Rho GTPases in growth cone guidance, it is important to determine their causal relationship in transducing guidance signal. (jneurosci.org)
  • Although, PAK-1/2 activation was observed during LPA-stimulated platelet shape change, PAKs are unlikely to be involved in LIMK-1 activation in these cells. (uni-muenchen.de)