Arhgef12

Summary

Gene Symbol: Arhgef12
Description: Rho guanine nucleotide exchange factor (GEF) 12
Alias: 2310014B11Rik, AU019857, Larg, mKIAA0382, rho guanine nucleotide exchange factor 12, leukemia-associated Rho guanine-nucleotide exchange factor, leukemia-associated RhoGEF
Species: mouse

Top Publications

  1. ncbi G12-G13-LARG-mediated signaling in vascular smooth muscle is required for salt-induced hypertension
    Angela Wirth
    Institute of Pharmacology, University of Heidelberg, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany
    Nat Med 14:64-8. 2008
  2. pmc Leukemia-associated Rho guanine nucleotide exchange factor promotes G alpha q-coupled activation of RhoA
    Michelle A Booden
    Department of Pharmacology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, 27599, USA
    Mol Cell Biol 22:4053-61. 2002
  3. pmc The Rho GEFs LARG and GEF-H1 regulate the mechanical response to force on integrins
    Christophe Guilluy
    Department of Cell and Developmental Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    Nat Cell Biol 13:722-7. 2011
  4. pmc Sphingosine 1-phosphate receptor 2 signals through leukemia-associated RhoGEF (LARG), to promote smooth muscle cell differentiation
    Matt D Medlin
    Department of Pathology, University of North Carolina, Chapel Hill, NC, USA
    Arterioscler Thromb Vasc Biol 30:1779-86. 2010
  5. doi Guanine nucleotide-binding proteins of the G12 family shape immune functions by controlling CD4+ T cell adhesiveness and motility
    Susanne Herroeder
    Institute of Pharmacology, University of Heidelberg, 69120 Heidelberg, Germany
    Immunity 30:708-20. 2009
  6. ncbi Plexin-B1 directly interacts with PDZ-RhoGEF/LARG to regulate RhoA and growth cone morphology
    Jakub M Swiercz
    Institute of Pharmacology, University of Heidelberg, Im Neuenheimer Feld 366, Germany
    Neuron 35:51-63. 2002
  7. pmc Leukemia-associated Rho guanine-nucleotide exchange factor is not critical for RhoA regulation, yet is important for platelet activation and thrombosis in mice
    C M Williams
    School of Physiology and Pharmacology, University of Bristol, Bristol, UK
    J Thromb Haemost 13:2102-7. 2015
  8. pmc RhoA and ROCK mediate histamine-induced vascular leakage and anaphylactic shock
    Constantinos M Mikelis
    Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nat Commun 6:6725. 2015
  9. pmc Jun kinase-induced overexpression of leukemia-associated Rho GEF (LARG) mediates sustained hypercontraction of longitudinal smooth muscle in inflammation
    Othman Al-Shboul
    Department of Physiology and Biophysics, VCU Program in Enteric Neuromuscular Sciences, Virginia Commonwealth University, Richmond, Virginia
    Am J Physiol Cell Physiol 306:C1129-41. 2014
  10. pmc Genetic dissection of plexin signaling in vivo
    Thomas Worzfeld
    Department of Pharmacology, Max Planck Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany
    Proc Natl Acad Sci U S A 111:2194-9. 2014

Scientific Experts

  • R Kuner
  • Hiroyuki Sakagami
  • Michelle A Booden
  • Stefan Offermanns
  • Constantinos M Mikelis
  • J Silvio Gutkind
  • Nina Wettschureck
  • Mikito Takefuji
  • Angela Wirth
  • C M Williams
  • Thomas Worzfeld
  • Shigetomo Fukuhara
  • Othman Al-Shboul
  • May Simaan
  • Jakub M Swiercz
  • Mykhaylo V Artamonov
  • Till F Althoff
  • Nicole Hajicek
  • Takako Negishi-Koga
  • Christophe Guilluy
  • Matt D Medlin
  • Susanne Herroeder
  • Osamu Katsumata
  • Yongquan Shi
  • Robert Grosse
  • Mikio Hoshino
  • Kozo Kaibuchi
  • Polyxeni Goulimari
  • Megan K Mulligan
  • Takeshi Yamada
  • Marina Zinovyeva
  • Brian Becknell
  • Masato Yoshizawa
  • Ralf H Adams
  • M T Harper
  • Andrius Masedunskas
  • A W Poole
  • Yi Zheng
  • Triantafyllos Chavakis
  • Koji Ando
  • Panomwat Amornphimoltham
  • R Goggs
  • Naoki Mochizuki
  • T G Walsh
  • Atsuko Sakurai
  • S Offermanns
  • Roberto Weigert
  • Karnam S Murthy
  • Jonathan A Epstein
  • Suhua Deng
  • Sunila Mahavadi
  • Brigitte Vollmar
  • John F Kuemmerle
  • Aycan Sentürk
  • Alexander Korostylev
  • Jingjing Xia
  • John R Grider
  • Ruizhe Zhou
  • Ancy D Nalli
  • Amparo Acker-Palmer
  • Divya P Kumar
  • Andrew M Chan
  • Berit Genz
  • David R Trentham
  • Paul W Read
  • Hiroki Chikumi
  • Hiroshi Yagi
  • Yoh suke Mukouyama
  • Daniel Martin
  • Kishor K Sivaraj
  • Andra Stevenson
  • Zygmunt S Derewenda
  • Urszula Derewenda
  • Thomas H Bugge
  • Avril V Somlyo
  • Rebeca Galisteo
  • Ko Momotani
  • Wenling Li
  • Todd R Palmby
  • Ruth Lyons
  • Roman Szabo
  • Marcus Kruger
  • Kerstin Troidl
  • Cong Tang
  • Julián Albarrán Juárez
  • Shengpeng Wang
  • Haruhiko Bito
  • Mikako Shirouzu
  • Roland H Friedel
  • Takaho Terada

Detail Information

Publications26

  1. ncbi G12-G13-LARG-mediated signaling in vascular smooth muscle is required for salt-induced hypertension
    Angela Wirth
    Institute of Pharmacology, University of Heidelberg, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany
    Nat Med 14:64-8. 2008
    ..of G12-G13, as well as of their major effector, the leukemia-associated Rho guanine nucleotide exchange factor (LARG), did not alter normal blood pressure regulation but did block the development of salt-induced hypertension...
  2. pmc Leukemia-associated Rho guanine nucleotide exchange factor promotes G alpha q-coupled activation of RhoA
    Michelle A Booden
    Department of Pharmacology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, 27599, USA
    Mol Cell Biol 22:4053-61. 2002
    Leukemia-associated Rho guanine-nucleotide exchange factor (LARG) belongs to the subfamily of Dbl homology RhoGEF proteins (including p115 RhoGEF and PDZ-RhoGEF) that possess amino-terminal regulator of G protein signaling (RGS) boxes ..
  3. pmc The Rho GEFs LARG and GEF-H1 regulate the mechanical response to force on integrins
    Christophe Guilluy
    Department of Cell and Developmental Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    Nat Cell Biol 13:722-7. 2011
    ..By combining biochemical and biophysical approaches, we identified two guanine nucleotide exchange factors (GEFs), LARG and GEF-H1, as key molecules that regulate the cellular adaptation to force...
  4. pmc Sphingosine 1-phosphate receptor 2 signals through leukemia-associated RhoGEF (LARG), to promote smooth muscle cell differentiation
    Matt D Medlin
    Department of Pathology, University of North Carolina, Chapel Hill, NC, USA
    Arterioscler Thromb Vasc Biol 30:1779-86. 2010
    ..The goals of this study were to identify the signaling pathway by which sphingosine 1-phosphate (S1P) activates RhoA in smooth muscle cells (SMC) and to evaluate the contribution of this pathway to the regulation of SMC phenotype...
  5. doi Guanine nucleotide-binding proteins of the G12 family shape immune functions by controlling CD4+ T cell adhesiveness and motility
    Susanne Herroeder
    Institute of Pharmacology, University of Heidelberg, 69120 Heidelberg, Germany
    Immunity 30:708-20. 2009
    ....
  6. ncbi Plexin-B1 directly interacts with PDZ-RhoGEF/LARG to regulate RhoA and growth cone morphology
    Jakub M Swiercz
    Institute of Pharmacology, University of Heidelberg, Im Neuenheimer Feld 366, Germany
    Neuron 35:51-63. 2002
    ..family members associate through their C termini with the Rho guanine nucleotide exchange factors PDZ-RhoGEF and LARG. Activation of plexin-B1 by semaphorin 4D regulates PDZ-RhoGEF/LARG activity leading to RhoA activation...
  7. pmc Leukemia-associated Rho guanine-nucleotide exchange factor is not critical for RhoA regulation, yet is important for platelet activation and thrombosis in mice
    C M Williams
    School of Physiology and Pharmacology, University of Bristol, Bristol, UK
    J Thromb Haemost 13:2102-7. 2015
    ..Leukemia-associated Rho guanine-nucleotide exchange factor (GEF [LARG]), a RhoA GEF, is highly expressed in platelets and may constitute a major upstream activator of RhoA...
  8. pmc RhoA and ROCK mediate histamine-induced vascular leakage and anaphylactic shock
    Constantinos M Mikelis
    Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nat Commun 6:6725. 2015
    ..This study supports a key role for the RhoA signalling circuitry in vascular permeability, thereby identifying novel pharmacological targets for many human diseases characterized by aberrant vascular leakage. ..
  9. pmc Jun kinase-induced overexpression of leukemia-associated Rho GEF (LARG) mediates sustained hypercontraction of longitudinal smooth muscle in inflammation
    Othman Al-Shboul
    Department of Physiology and Biophysics, VCU Program in Enteric Neuromuscular Sciences, Virginia Commonwealth University, Richmond, Virginia
    Am J Physiol Cell Physiol 306:C1129-41. 2014
    ..In control longitudinal smooth muscle cells, ACh acting via m3 receptors activated sequentially Gα12, RhoGEF (LARG), and the RhoA/Rho kinase pathway...
  10. pmc Genetic dissection of plexin signaling in vivo
    Thomas Worzfeld
    Department of Pharmacology, Max Planck Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany
    Proc Natl Acad Sci U S A 111:2194-9. 2014
    ..Our genetic analyses uncover the in vivo context-dependence and functional specificity of individual plexin-mediated signaling pathways during development. ..
  11. pmc Agonist-induced Ca2+ sensitization in smooth muscle: redundancy of Rho guanine nucleotide exchange factors (RhoGEFs) and response kinetics, a caged compound study
    Mykhaylo V Artamonov
    From the Departments of Molecular Physiology and Biological Physics and
    J Biol Chem 288:34030-40. 2013
    ..of guanine nucleotide exchange factors (RhoGEFs), which includes PDZ-RhoGEF (PRG) and leukemia-associated RhoGEF (LARG). However, their contributions to Ca(2+)-sensitized force are not well understood...
  12. pmc Procontractile G protein-mediated signaling pathways antagonistically regulate smooth muscle differentiation in vascular remodeling
    Till F Althoff
    Department of Pharmacology, Max Planck Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany
    J Exp Med 209:2277-90. 2012
    ..In mice lacking Gα(12)/Gα(13) or their effector, the RhoGEF protein LARG, RhoA-dependent SRF-regulation was blocked and down-regulation of VSMC differentiation marker genes was enhanced...
  13. pmc PDZ-RhoGEF and LARG are essential for embryonic development and provide a link between thrombin and LPA receptors and Rho activation
    Constantinos M Mikelis
    Oral and Pharyngeal Cancer Branch, NIDCR, Genetics and Developmental Biology Center, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 288:12232-43. 2013
    ..been proposed to link Gα12/13 GPCRs to Rho activation, including PDZ-RhoGEF (PRG), leukemia-associated Rho GEF (LARG), p115-RhoGEF (p115), lymphoid blast crisis (Lbc), and Dbl...
  14. pmc RhoGEF12 controls cardiac remodeling by integrating G protein- and integrin-dependent signaling cascades
    Mikito Takefuji
    Department of Pharmacology, Max Planck Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany
    J Exp Med 210:665-73. 2013
    ..Collectively, RhoGEF12 acts as an integrator of stretch-induced signaling cascades in cardiomyocytes and is an interesting new target for therapeutic intervention in patients with pressure overload-induced heart failure...
  15. doi The mDial formin is required for neutrophil polarization, migration, and activation of the LARG/RhoA/ROCK signaling axis during chemotaxis
    Yongquan Shi
    Department of Medicine, Samuel Lunenfeld and Toronto Hospital Research Institutes, University of Toronto, Toronto, Canada
    J Immunol 182:3837-45. 2009
    ..coil-containing protein kinase (ROCK), and the leukemia-associated RhoA guanine nucleotide exchange factor (LARG)...
  16. doi IQ-ArfGEF/BRAG1 is a guanine nucleotide exchange factor for Arf6 that interacts with PSD-95 at postsynaptic density of excitatory synapses
    Hiroyuki Sakagami
    Department of Anatomy, Kitasato University School of Medicine, Sagamihara 228 8555, Japan
    Neurosci Res 60:199-212. 2008
    ..Taken together, IQ-ArfGEF/BRAG1 forms a postsynaptic protein complex containing PSD-95 and NMDA receptors at excitatory synapses, where it may function as a GEF for Arf6...
  17. doi IQ-ArfGEF/BRAG1 is associated with synaptic ribbons in the mouse retina
    Osamu Katsumata
    Department of Anatomy, Kitasato University School of Medicine, Sagamihara, Kanagawa 228 8555, Japan
    Eur J Neurosci 30:1509-16. 2009
    ..These findings indicate that IQ-ArfGEF/BRAG1 is a novel component of retinal synaptic ribbons and forms a protein complex with RIBEYE...
  18. pmc LARG and mDia1 link Galpha12/13 to cell polarity and microtubule dynamics
    Polyxeni Goulimari
    Institute of Pharmacology, University of Heidelberg, 69120 Heidelberg, Germany
    Mol Biol Cell 19:30-40. 2008
    ..Cell polarization involves the Galpha(12/13)-interacting leukemia-associated RhoGEF (LARG) and the actin-nucleating diaphanous formin mDia1...
  19. pmc Identification of critical residues in G(alpha)13 for stimulation of p115RhoGEF activity and the structure of the G(alpha)13-p115RhoGEF regulator of G protein signaling homology (RH) domain complex
    Nicole Hajicek
    Department of Pharmacology, College of Medicine, University of Illinois, Chicago, Illinois 60612, USA
    J Biol Chem 286:20625-36. 2011
    ..Taken together, these data provide new insight into the mechanism by which p115RhoGEF is activated by Gα(13)...
  20. pmc Toward understanding the genetics of alcohol drinking through transcriptome meta-analysis
    Megan K Mulligan
    Waggoner Center for Alcohol and Addiction Research and Sections of Neurobiology, University of Texas, Austin, TX 78712, USA
    Proc Natl Acad Sci U S A 103:6368-73. 2006
    ..cis-regulated candidate genes for an alcohol preference quantitative trait locus on chromosome 9 were identified: Arhgef12, Carm1, Cryab, Cox5a, Dlat, Fxyd6, Limd1, Nicn1, Nmnat3, Pknox2, Rbp1, Sc5d, Scn4b, Tcf12, Vps11, and Zfp291 and ..
  21. doi Suppression of bone formation by osteoclastic expression of semaphorin 4D
    Takako Negishi-Koga
    Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
    Nat Med 17:1473-80. 2011
    ..Notably, Sema4D-specific antibody treatment markedly prevented bone loss in a model of postmenopausal osteoporosis. Thus, Sema4D has emerged as a new therapeutic target for the discovery and development of bone-increasing drugs...
  22. ncbi Physical and functional interactions of the lysophosphatidic acid receptors with PDZ domain-containing Rho guanine nucleotide exchange factors (RhoGEFs)
    Takeshi Yamada
    School of Allied Health Sciences, Faculty of Medicine, Osaka University, Yamadaoka, Suita Shi, Osaka 565 0871, Japan
    J Biol Chem 280:19358-63. 2005
    ..of LPA1 and LPA2 but not LPA3 interact with the PDZ domains of PDZ domain-containing RhoGEFs, PDZ-RhoGEF, and LARG, which are comprised of PDZ, RGS, Dbl homology (DH), and pleckstrin homology (PH) domains...
  23. ncbi Molecular cloning, sequence and expression pattern analysis of the mouse orthologue of the leukemia-associated guanine nucleotide exchange factor
    Marina Zinovyeva
    Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia
    Gene 337:181-8. 2004
    ..Recently, a novel member of the Dbl family, leukemia-associated Rho GEF factor (LARG), has been reported to be a fusion partner with mixed-lineage leukemia (MLL) protein in the acute myeloid leukemia, ..
  24. ncbi Characterization of leukemia-associated Rho guanine nucleotide exchange factor (LARG) expression during murine development
    Brian Becknell
    Integrated Biomedical Science Graduate Program, College of Medicine and Public Health, The Ohio State University, OH 43210, USA
    Cell Tissue Res 314:361-6. 2003
    LARG (leukemia-associated Rho guanine nucleotide exchange factor, ARHGEF12) was originally identified as a fusion partner of the MLL gene at 11q23 in human acute myeloid leukemia...
  25. ncbi Dynamic and coordinated expression profile of dbl-family guanine nucleotide exchange factors in the developing mouse brain
    Masato Yoshizawa
    Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Yoshidakonoe cho, 606 8501 Kyoto, Japan
    Gene Expr Patterns 3:375-81. 2003
    ..Our study reveals the dynamic and coordinated expression profiles of the Dbl-GEFs and provides a basic framework for understanding the function of GEFs in neural development...
  26. ncbi Characterization of the expression of PDZ-RhoGEF, LARG and G(alpha)12/G(alpha)13 proteins in the murine nervous system
    R Kuner
    Department of Molecular Pharmacology, Institute for Pharmacology, Im Neuenheimer Feld 366, University of Heidelberg, Germany
    Eur J Neurosci 16:2333-41. 2002
    ..Recently, two novel Rho-specific guanine nucleotide exchange factors (RhoGEFs), PDZ-RhoGEF and LARG, have been identified to interact with the activated alpha-subunits of G12/G13 and are thus believed to mediate ..