2,742 results match your criteria ras rho

The Composite of 3, 4-Dihydroxyl-Phenyl Lactic Acid and Notoginsenoside R1 Attenuates Myocardial Ischemia and Reperfusion Injury Through Regulating Mitochondrial Respiratory Chain.

Front Physiol 2021 12;12:538962. Epub 2021 Jul 12.

Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China.

Aim: 3,4-Dihydroxyl-phenyl lactic acid (DLA) and notoginsenoside R1 (R1) are known to protect ischemia and reperfusion (I/R) injury by targeting Sirtuin1/NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 10/the Mitochondrial Complex I (Sirt-1/NDUFA10/Complex I) and Rho-associated kinase/adenosine triphosphate (ROCK/ATP) ATP synthase δ subunit (ATP 5D), respectively. We hypothesized that a composite of the two may exhibit a more potent effect on I/R injury. The study was designed to test this hypothesis. Read More

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Regulation of Leukaemia Associated Rho GEF (LARG/ARHGEF12).

Small GTPases 2021 Jul 25:1-9. Epub 2021 Jul 25.

Cancer Biology Program, University of Hawaii Cancer Center, University of Hawaii at Mānoa, Honolulu, USA.

The Ras homologous (Rho) protein family of GTPases (RhoA, RhoB and RhoC) are the members of the Ras superfamily and regulate cellular processes such as cell migration, proliferation, polarization, adhesion, gene transcription and cytoskeletal structure. Rho GTPases function as molecular switches that cycle between GTP-bound (active state) and GDP-bound (inactive state) forms. Leukaemia-associated RhoGEF (LARG) is a guanine nucleotide exchange factor (GEF) that activates RhoA subfamily GTPases by promoting the exchange of GDP for GTP. Read More

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An variant links aberrant Rac1 function to early-onset skeletal fragility.

JBMR Plus 2021 Jul 7;5(7):e10509. Epub 2021 Jun 7.

Folkhälsan Institute of Genetics Helsinki Finland.

Ras homologous guanosine triphosphatases (RhoGTPases) control several cellular functions, including cytoskeletal actin remodeling and cell migration. Their activities are downregulated by GTPase-activating proteins (GAPs). Although RhoGTPases are implicated in bone remodeling and osteoclast and osteoblast function, their significance in human bone health and disease remains elusive. Read More

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Fasudil prevents liver fibrosis activating natural killer cells and suppressing hepatic stellate cells.

World J Gastroenterol 2021 Jun;27(24):3581-3594

Institute of Immunopharmaceutical Sciences, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, Shandong Province, China.

Background: Fasudil, as a Ras homology family member A (RhoA) kinase inhibitor, is used to improve brain microcirculation and promote nerve regeneration clinically. Increasing evidence shows that Rho-kinase inhibition could improve liver fibrosis.

Aim: To evaluate the anti-fibrotic effects of Fasudil in a mouse model of liver fibrosis induced by thioacetamide (TAA). Read More

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SmgGDS: An Emerging Master Regulator of Prenylation and Trafficking by Small GTPases in the Ras and Rho Families.

Front Mol Biosci 2021 16;8:685135. Epub 2021 Jun 16.

Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI, United States.

Newly synthesized small GTPases in the Ras and Rho families are prenylated by cytosolic prenyltransferases and then escorted by chaperones to membranes, the nucleus, and other sites where the GTPases participate in a variety of signaling cascades. Understanding how prenylation and trafficking are regulated will help define new therapeutic strategies for cancer and other disorders involving abnormal signaling by these small GTPases. A growing body of evidence indicates that splice variants of SmgGDS (gene name RAP1GDS1) are major regulators of the prenylation, post-prenylation processing, and trafficking of Ras and Rho family members. Read More

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Small Rho GTPases and their associated RhoGEFs mutations promote immunological defects in primary immunodeficiencies.

Int J Biochem Cell Biol 2021 Aug 1;137:106034. Epub 2021 Jul 1.

Bioprocess Technology Division, School of Industrial Technology, Universiti Sains Malaysia, Gelugor, Penang, 11800, Malaysia. Electronic address:

Primary immunodeficiencies (PIDs) are associated with deleterious mutations of genes that encode proteins involved in actin cytoskeleton reorganisation. This deficiency affects haematopoietic cells. PID results in the defective function of immune cells, such as impaired chemokine-induced motility, receptor signalling, development and maturation. Read More

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Emerging Roles of Small GTPases in Islet β-Cell Function.

Cells 2021 Jun 15;10(6). Epub 2021 Jun 15.

Department of Molecular and Cellular Endocrinology, Arthur Riggs Diabetes & Metabolism Research Institute, City of Hope Beckman Research Institute, Duarte, CA 91010, USA.

Several small guanosine triphosphatases (GTPases) from the Ras protein superfamily regulate glucose-stimulated insulin secretion in the pancreatic islet β-cell. The Rho family GTPases Cdc42 and Rac1 are primarily involved in relaying key signals in several cellular functions, including vesicle trafficking, plasma membrane homeostasis, and cytoskeletal dynamics. They orchestrate specific changes at each spatiotemporal region within the β-cell by coordinating with signal transducers, guanine nucleotide exchange factors (GEFs), GTPase-activating factors (GAPs), and their effectors. Read More

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Loss function of Bcr mutation causes gastrointestinal dysmotility and brain developmental defects.

Neurogastroenterol Motil 2021 Jun 30:e14190. Epub 2021 Jun 30.

Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China.

Background: The breakpoint cluster region (BCR) is a protein that originally forms a fusion protein with c-Abl tyrosine kinase and induces leukemia. Researchers have shown that BCR is enriched in the central nervous system and may contribute to neurological disorders. We aimed to investigate the physiological function of BCR in neural development in the gastrointestinal (GI) tract and brain. Read More

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The small GTP-binding protein TaRop10 interacts with TaTrxh9 and functions as a negative regulator of wheat resistance against the stripe rust.

Plant Sci 2021 Aug 14;309:110937. Epub 2021 May 14.

State Key Laboratory of Crop Stress Biology for Arid Areas, College of Plant Protection, Northwest A&F University, Yangling, Shaanxi 712100, China. Electronic address:

Small GTP-binding proteins, also known as ROPs (Rho of Plants), are a subfamily of the Ras superfamily of signaling G-proteins and are required for numerous signaling processes, ranging from growth and development to biotic and abiotic signaling. In this study, we cloned and characterized wheat TaRop10, a homolog of Arabidopsis ROP10 and member of the class II ROP, and uncovered a role for TaRop10 in wheat response to Puccinia striiformis f. sp. Read More

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Wnt5a modulates dendritic spine dynamics through the regulation of Cofilin via small Rho GTPase activity in hippocampal neurons.

J Neurochem 2021 Jun 9. Epub 2021 Jun 9.

Centro de Envejecimiento y Regeneración (CARE), Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.

Dendritic spines are small, actin-rich protrusions that act as the receiving sites of most excitatory inputs in the central nervous system. The remodeling of the synapse architecture is mediated by actin cytoskeleton dynamics, a process precisely regulated by the small Rho GTPase family. Wnt ligands exert their presynaptic and postsynaptic effects during formation and consolidation of the synaptic structure. Read More

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Progress in the therapeutic inhibition of Cdc42 signalling.

Biochem Soc Trans 2021 Jun;49(3):1443-1456

Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, U.K.

Cdc42 is a member of the Rho family of small GTPases and a key regulator of the actin cytoskeleton, controlling cell motility, polarity and cell cycle progression. It signals downstream of the master regulator Ras and is essential for cell transformation by this potent oncogene. Overexpression of Cdc42 is observed in several cancers, where it is linked to poor prognosis. Read More

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The to and fro of Rho.

Structure 2021 Jun;29(6):507-509

Department of Biochemistry, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA; Department of Radiation Oncology, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA. Electronic address:

The functions of Ras members are largely governed by the structural dynamics of the nucleotide-binding switch regions. In this issue of Structure, Lin et al. (2021) take a close look at the dynamic equilibrium of RhoA, the founding member of the Rho family of Ras GTPases. Read More

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Rac1, A Potential Target for Tumor Therapy.

Front Oncol 2021 17;11:674426. Epub 2021 May 17.

Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.

RAS-related C3 botulinum toxin substrate 1 (Rac.1) is one of the important members of Rho GTPases. It is well known that Rac1 is a cytoskeleton regulation protein that regulates cell adhesion, morphology, and movement. Read More

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The Crossroads between RAS and RHO Signaling Pathways in Cellular Transformation, Motility and Contraction.

Genes (Basel) 2021 May 27;12(6). Epub 2021 May 27.

Tumour-Stroma Signalling Laboratory, Centro de Investigación del Cáncer and Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC)-University of Salamanca, 37007 Salamanca, Spain.

Ras and Rho proteins are GTP-regulated molecular switches that control multiple signaling pathways in eukaryotic cells. Ras was among the first identified oncogenes, and it appears mutated in many forms of human cancer. It mainly promotes proliferation and survival through the MAPK pathway and the PI3K/AKT pathways, respectively. Read More

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Characterization and Pharmacological Inhibition of the Pore-Forming CDTb Toxin.

Toxins (Basel) 2021 05 28;13(6). Epub 2021 May 28.

Institute of Pharmacology and Toxicology, Ulm University Medical Center, 89081 Ulm, Germany.

The clinically highly relevant releases several AB-type toxins that cause diseases such as diarrhea and pseudomembranous colitis. In addition to the main virulence factors Rho/Ras-glycosylating toxins TcdA and TcdB, hypervirulent strains produce the binary AB-type toxin CDT. CDT consists of two separate proteins. Read More

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RLIP76: A Structural and Functional Triumvirate.

Cancers (Basel) 2021 May 4;13(9). Epub 2021 May 4.

Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, UK.

RLIP76/RalBP1 is an ATP-dependent transporter of glutathione conjugates, which is overexpressed in various human cancers, but its diverse functions in normal cells, which include endocytosis, stress response and mitochondrial dynamics, are still not fully understood. The protein can be divided into three distinct regions, each with its own structural properties. At the centre of the protein are two well-defined domains, a GTPase activating protein domain targeting Rho family small G proteins and a small coiled-coil that binds to the Ras family small GTPases RalA and RalB. Read More

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Pharmacological Modulators of Small GTPases of Rho Family in Neurodegenerative Diseases.

Front Cell Neurosci 2021 12;15:661612. Epub 2021 May 12.

Department of Anatomy and Cell Biology, The Harriet and John Wooten Laboratory for Alzheimer's and Neurogenerative Diseases Research, Brody School of Medicine, East Carolina University, Greenville, NC, United States.

Classical Rho GTPases, including RhoA, Rac1, and Cdc42, are members of the Ras small GTPase superfamily and play essential roles in a variety of cellular functions. Rho GTPase signaling can be turned on and off by specific GEFs and GAPs, respectively. These features empower Rho GTPases and their upstream and downstream modulators as targets for scientific research and therapeutic intervention. Read More

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PD-L1 recruits phospholipase C and enhances tumorigenicity of lung tumors harboring mutant forms of EGFR.

Cell Rep 2021 May;35(8):109181

Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel. Electronic address:

Cancer immunotherapy focuses on inhibitors of checkpoint proteins, such as programmed death ligand 1 (PD-L1). Unlike RAS-mutated lung cancers, EGFR mutant tumors have a generally low response to immunotherapy. Because treatment outcomes vary by EGFR allele, intrinsic and microenvironmental factors may be involved. Read More

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Protocol for structural and biochemical analyses of RhoA GTPase.

STAR Protoc 2021 Jun 14;2(2):100541. Epub 2021 May 14.

Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.

Ras GTPases in complex with Guanosine triphosphate (GTP) or GTP analog exhibit dynamic equilibrium between two interconvertible conformations-an inactive state 1 and an active state 2. Unlike Ras, it remains unclear if the GTP-bound form of Rho GTPases also exhibits multiple conformational states. Here, we describe a protocol for structural and biochemical analyses of RhoA GTPase. Read More

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Extracellular vesicles derived from mesenchymal stem cells containing microRNA-381 protect against spinal cord injury in a rat model via the BRD4/WNT5A axis.

Bone Joint Res 2021 May;10(5):328-339

The Affiliated Hospital of Southwest Medical University, Luzhou, China.

Aims: Non-coding microRNA (miRNA) in extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) may promote neuronal repair after spinal cord injury (SCI). In this paper we report on the effects of MSC-EV-microRNA-381 (miR-381) in a rodent model of SCI.

Methods: In the current study, the luciferase assay confirmed a binding site of bromodomain-containing protein 4 (BRD4) and Wnt family member 5A (WNT5A). Read More

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Genes associated with amyloid-beta-induced inflammasome-mediated neuronal death identified using functional gene trap mutagenesis approach.

Int J Biochem Cell Biol 2021 Jul 19;136:106014. Epub 2021 May 19.

Institute for Research, Development and Innovation, International Medical University, Kuala Lumpur, Malaysia. Electronic address:

Alzheimer's disease is an irreversible neurodegenerative disease, which accounts for most dementia cases. Neuroinflammation is increasingly recognised for its roles in Alzheimer's disease pathogenesis which, in part, links amyloid-beta to neuronal death. Neuroinflammatory signalling can be exhibited by neurons themselves, potentially leading to widespread neuronal cell death, although neuroinflammation is commonly associated with glial cells. Read More

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Emerging role of lncRNAs in the regulation of Rho GTPase pathway.

Biomed Pharmacother 2021 Aug 17;140:111731. Epub 2021 May 17.

Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

The Ras homolog (Rho) family of small GTPases comprise several proteins with prominent roles in regulation of cell cycle transition, cell migration, and remodeling of actin cytoskeleton. Expression of these proteins is regulated by several factors among them are long non-coding RNAs (lncRNAs). The impact of lncRNAs on Rho GTPases signaling can be exerted through direct modulation of expression of these proteins or influencing expression of miRNAs that negatively regulate Rho GTPases. Read More

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Active GTPase Pulldown Protocol.

Methods Mol Biol 2021 ;2262:117-135

Institute of Molecular Cell Biology, Center for Molecular Biomedicine, University Hospital Jena, Jena, Germany.

Ras and its related small GTPases are important signalling nodes that regulate a wide variety of cellular functions. The active form of these proteins exists in a transient GTP bound state that mediates downstream signalling events. The dysregulation of these GTPases has been associated with the progression of multiple diseases, most prominently cancer and developmental syndromes known as Rasopathies. Read More

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The Small GTPases in Fungal Signaling Conservation and Function.

Cells 2021 Apr 28;10(5). Epub 2021 Apr 28.

Laboratorio de Genómica Funcional y Comparativa, División de Biología Molecular, IPICYT, San Luis Potosí 78216, Mexico.

Monomeric GTPases, which belong to the Ras superfamily, are small proteins involved in many biological processes. They are fine-tuned regulated by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). Several families have been identified in organisms from different kingdoms. Read More

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Inhibition of the Myocardin-Related Transcription Factor Pathway Increases Efficacy of Trametinib in -Mutant Melanoma Cell Lines.

Cancers (Basel) 2021 Apr 22;13(9). Epub 2021 Apr 22.

Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824, USA.

The Ras/MEK/ERK pathway has been the primary focus of targeted therapies in melanoma; it is aberrantly activated in almost 80% of human cutaneous melanomas (≈50% V600 mutations and ≈30% mutations). While drugs targeting the MAPK pathway have yielded success in V600 mutant melanoma patients, such therapies have been ineffective in patients with mutant melanomas in part due to their cytostatic effects and primary resistance. Here, we demonstrate that increased Rho/MRTF-pathway activation correlates with high intrinsic resistance to the MEK inhibitor, trametinib, in a panel of mutant melanoma cell lines. Read More

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Hidden Targets in RAF Signalling Pathways to Block Oncogenic RAS Signalling.

Genes (Basel) 2021 04 10;12(4). Epub 2021 Apr 10.

Systems Biology Ireland, School of Medicine, University College Dublin, Belfield, Dublin 4, Ireland.

Oncogenic RAS (Rat sarcoma) mutations drive more than half of human cancers, and RAS inhibition is the holy grail of oncology. Thirty years of relentless efforts and harsh disappointments have taught us about the intricacies of oncogenic RAS signalling that allow us to now get a pharmacological grip on this elusive protein. The inhibition of effector pathways, such as the RAF-MEK-ERK pathway, has largely proven disappointing. Read More

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RhoA: a dubious molecule in cardiac pathophysiology.

J Biomed Sci 2021 Apr 28;28(1):33. Epub 2021 Apr 28.

Department of Internal Medicine III (Cardiology, Angiology, Intensive Care), University Medical Center Kiel, Rosalind-Franklin Str. 12, 24105, Kiel, Germany.

The Ras homolog gene family member A (RhoA) is the founding member of Rho GTPase superfamily originally studied in cancer cells where it was found to stimulate cell cycle progression and migration. RhoA acts as a master switch control of actin dynamics essential for maintaining cytoarchitecture of a cell. In the last two decades, however, RhoA has been coined and increasingly investigated as an essential molecule involved in signal transduction and regulation of gene transcription thereby affecting physiological functions such as cell division, survival, proliferation and migration. Read More

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Bacterial RTX toxins and host immunity.

Curr Opin Infect Dis 2021 Jun;34(3):187-196

Laboratory of Molecular Biology of Bacterial Pathogens, Institute of Microbiology of the Czech Academy of Sciences, Vídeňská 1083, Prague, Czech Republic.

Purpose Of Review: RTX toxin action often defines the outcome of bacterial infections. Here, we discuss the progress in understanding the impacts of RTX toxin activities on host immunity.

Recent Findings: Bordetella pertussis CyaA activity paralyzes sentinel phagocytic cells by elevating cellular cAMP levels and blocks differentiation of infiltrating monocytes into bactericidal macrophages, promoting also de-differentiation of resident alveolar macrophages into monocyte-like cells. Read More

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Circulating Angiotensin-(1-7) Is Reduced in Alzheimer's Disease Patients and Correlates With White Matter Abnormalities: Results From a Pilot Study.

Front Neurosci 2021 6;15:636754. Epub 2021 Apr 6.

Laboratório Interdisciplinar de Investigação Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil.

Introduction: Alzheimer's disease (AD) is the leading cause of dementia worldwide. Despite the extensive research, its pathophysiology remains largely unelucidated. Currently, more attention is being given to the disease's vascular and inflammatory aspects. Read More

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Distinct signaling by insulin and IGF-1 receptors and their extra- and intracellular domains.

Proc Natl Acad Sci U S A 2021 Apr;118(17)

Section of Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215;

Insulin and insulin-like growth factor 1 (IGF-1) receptors share many downstream signaling pathways but have unique biological effects. To define the molecular signals contributing to these distinct activities, we performed global phosphoproteomics on cells expressing either insulin receptor (IR), IGF-1 receptor (IGF1R), or chimeric IR-IGF1R receptors. We show that IR preferentially stimulates phosphorylations associated with mammalian target of rapamycin complex 1 (mTORC1) and Akt pathways, whereas IGF1R preferentially stimulates phosphorylations on proteins associated with the Ras homolog family of guanosine triphosphate hydrolases (Rho GTPases), and cell cycle progression. Read More

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