Gene Symbol: CYTH2
Description: cytohesin 2
Alias: ARNO, CTS18, CTS18.1, PSCD2, PSCD2L, SEC7L, Sec7p-L, Sec7p-like, cytohesin-2, cytohesin-2, ARF exchange factor, ARF nucleotide-binding site opener, CTC-273B12.8, PH, SEC7 and coiled-coil domain-containing protein 2, pleckstrin homology, Sec7 and coiled-coil domains 2, pleckstrin homology, Sec7 and coiled/coil domains 2 (cytohesin-2)
Species: human
Products:     CYTH2

Top Publications

  1. Mansour M, Lee S, Pohajdak B. The N-terminal coiled coil domain of the cytohesin/ARNO family of guanine nucleotide exchange factors interacts with the scaffolding protein CASP. J Biol Chem. 2002;277:32302-9 pubmed
    ..All of the members of the cytohesin family (including ARNO, ARNO3, and the newly characterized cytohesin-4) have a similar domain distribution consisting of a Sec7 homology ..
  2. Kitano J, Kimura K, Yamazaki Y, Soda T, Shigemoto R, Nakajima Y, et al. Tamalin, a PDZ domain-containing protein, links a protein complex formation of group 1 metabotropic glutamate receptors and the guanine nucleotide exchange factor cytohesins. J Neurosci. 2002;22:1280-9 pubmed
    ..The results indicate that tamalin plays a key role in the association of group 1 mGluRs with the ARF-specific GEF proteins and contributes to intracellular trafficking and the macromolecular organization of group 1 mGluRs at synapses. ..
  3. Santy L, Frank S, Hatfield J, Casanova J. Regulation of ARNO nucleotide exchange by a PH domain electrostatic switch. Curr Biol. 1999;9:1173-6 pubmed
    b>ARNO is a member of a family of guanine nucleotide exchange factors that activate small GTPases called ADP-ribosylation factors (ARFs) [1] [2] [3], which regulate vesicular trafficking and, in one case (ARF6), also regulate cortical actin ..
  4. Stalder D, Barelli H, Gautier R, Macia E, Jackson C, Antonny B. Kinetic studies of the Arf activator Arno on model membranes in the presence of Arf effectors suggest control by a positive feedback loop. J Biol Chem. 2011;286:3873-83 pubmed publisher
    Proteins of the cytohesin/Arno/Grp1 family of Arf activators are positive regulators of the insulin-signaling pathway and control various remodeling events at the plasma membrane...
  5. Meacci E, Tsai S, Adamik R, Moss J, Vaughan M. Cytohesin-1, a cytosolic guanine nucleotide-exchange protein for ADP-ribosylation factor. Proc Natl Acad Sci U S A. 1997;94:1745-8 pubmed
    ..In this regard, it differs from a recently reported BFA-sensitive ARF-GEP that contains a Sec7 domain. ..
  6. Frank S, Upender S, Hansen S, Casanova J. ARNO is a guanine nucleotide exchange factor for ADP-ribosylation factor 6. J Biol Chem. 1998;273:23-7 pubmed
    ..Like other GTPases, ARF activation is facilitated by specific guanine nucleotide exchange factors (GEFs). ARNO (ARF nucleotide-binding site opener) is a member of a growing family of ARF-GEFs that share a common, tripartite ..
  7. Shmuel M, Santy L, Frank S, Avrahami D, Casanova J, Altschuler Y. ARNO through its coiled-coil domain regulates endocytosis at the apical surface of polarized epithelial cells. J Biol Chem. 2006;281:13300-8 pubmed
    b>ARNO is a guanine-nucleotide exchange protein for the ARF family of GTPases. Here we show that in polarized epithelial cells, ARNO is localized exclusively to the apical plasma membrane, where it regulates endocytosis...
  8. Venkateswarlu K, Oatey P, Tavare J, Cullen P. Insulin-dependent translocation of ARNO to the plasma membrane of adipocytes requires phosphatidylinositol 3-kinase. Curr Biol. 1998;8:463-6 pubmed
    ..b>ARNO is a member of the family of guanine nucleotide exchange factors for ARFs which includes cytohesin-1 and GRP-1 [2] [..
  9. Zhu W, London N, Gibson C, Davis C, Tong Z, Sorensen L, et al. Interleukin receptor activates a MYD88-ARNO-ARF6 cascade to disrupt vascular stability. Nature. 2012;492:252-5 pubmed publisher
    ..the result of signalling through the small GTPase ADP-ribosylation factor 6 (ARF6) and its activator ARF nucleotide binding site opener (ARNO; also known as CYTH2)...

More Information


  1. Chardin P, Paris S, Antonny B, Robineau S, Beraud Dufour S, Jackson C, et al. A human exchange factor for ARF contains Sec7- and pleckstrin-homology domains. Nature. 1996;384:481-4 pubmed
    ..Its activation is controlled by as-yet unidentified guanine-nucleotide exchange factors. Gea1, the first ARF exchange factor to be discovered in yeast, is a large protein containing a domain of homology with Sec7, another yeast ..
  2. Venkateswarlu K. Interaction protein for cytohesin exchange factors 1 (IPCEF1) binds cytohesin 2 and modifies its activity. J Biol Chem. 2003;278:43460-9 pubmed
    ..Using cytohesin 2 as bait in yeast two-hybrid screening, we have isolated a cDNA encoding a protein termed interaction protein ..
  3. Hofmann I, Thompson A, Sanderson C, Munro S. The Arl4 family of small G proteins can recruit the cytohesin Arf6 exchange factors to the plasma membrane. Curr Biol. 2007;17:711-6 pubmed
    ..and cell adhesion, and one of its major activators is the exchange factor Arf nucleotide-binding site opener (ARNO), also called cytohesin-2 [1, 2]...
  4. Macia E, Paris S, Chabre M. Binding of the PH and polybasic C-terminal domains of ARNO to phosphoinositides and to acidic lipids. Biochemistry. 2000;39:5893-901 pubmed
    The activity on ARF of the guanine nucleotide exchange factor ARNO depends on its membrane recruitment, induced by binding of its PH domain to phosphoinositides...
  5. Boehm T, Hofer S, Winklehner P, Kellersch B, Geiger C, Trockenbacher A, et al. Attenuation of cell adhesion in lymphocytes is regulated by CYTIP, a protein which mediates signal complex sequestration. EMBO J. 2003;22:1014-24 pubmed
    ..These findings outline a novel mechanism of signal chain abrogation through sequestration of a limiting component by specific protein-protein interactions. ..
  6. Valsecchi S, Rusconi M, Mazzoni M, Viviano G, Pagnotta R, Zaghi C, et al. Occurrence and sources of perfluoroalkyl acids in Italian river basins. Chemosphere. 2015;129:126-34 pubmed publisher
    ..Among the rivers directly flowing into the sea, Brenta, Po and Arno present significant concentrations, while concentrations in Tevere and Adige, which are not impacted by relevant ..
  7. Mendonça L, Ocarino J, Bittencourt N, Santos T, Barreto R, Fonseca S. Normative data of frontal plane patellar alignment in athletes. Phys Ther Sport. 2015;16:148-53 pubmed publisher
    ..of this study was to provide normative data of frontal plane patellar alignment according to McConnell and Arno angles, verify the association between theses angles and identify the presence of patellar rotation in different ..
  8. Guaraldi G, Zona S, Brothers T, Carli F, Stentarelli C, Dolci G, et al. Aging with HIV vs. HIV seroconversion at older age: a diverse population with distinct comorbidity profiles. PLoS ONE. 2015;10:e0118531 pubmed publisher
    ..Patients were matched in a 1:3 ratio with controls from the CINECA ARNO database. MM was defined as the concurrent presence of >2 NICM...
  9. Disoteo O, Grimaldi F, Papini E, Attanasio R, Tonutti L, Pellegrini M, et al. State-of-the-Art Review on Diabetes Care in Italy. Ann Glob Health. 2015;81:803-13 pubmed publisher
    ..In Italy, the status of diabetes care is being monitored using the data from 2 permanent observatories: the ARNO Observatory Diabetes and the Associazione Medici Diabetologi Annals...
  10. Pagano E, De Rosa M, Rossi E, Cinconze E, Marchesini G, Miccoli R, et al. The relative burden of diabetes complications on healthcare costs: The population-based CINECA-SID ARNO Diabetes Observatory. Nutr Metab Cardiovasc Dis. 2016;26:944-50 pubmed publisher
    ..retrospective cohort of residents in four Italian areas that were served by Local Health Units participating in the ARNO Observatory...
  11. Lowery J, Szul T, Seetharaman J, Jian X, Su M, Forouhar F, et al. Novel C-terminal motif within Sec7 domain of guanine nucleotide exchange factors regulates ADP-ribosylation factor (ARF) binding and activation. J Biol Chem. 2011;286:36898-906 pubmed publisher
    ..and/or Sec7d of two large brefeldin A-sensitive GEFs (GBF1 and BIG2) and one small brefeldin A-resistant GEF (ARNO) that abrogated binding of ARF and a single alanine substitution that allowed ARF binding but inhibited GDP to GTP ..
  12. Jayaram B, Syed I, Kyathanahalli C, Rhodes C, Kowluru A. Arf nucleotide binding site opener [ARNO] promotes sequential activation of Arf6, Cdc42 and Rac1 and insulin secretion in INS 832/13 β-cells and rat islets. Biochem Pharmacol. 2011;81:1016-27 pubmed publisher
    ..Herein, we tested the hypothesis that Arf nucleotide binding site opener [ARNO], a guanine nucleotide-exchange factor [GEF] for the small G-protein Arf6, mediates the ..
  13. Charles R, Namkung Y, Cotton M, Laporte S, Claing A. β-Arrestin-mediated Angiotensin II Signaling Controls the Activation of ARF6 Protein and Endocytosis in Migration of Vascular Smooth Muscle Cells. J Biol Chem. 2016;291:3967-81 pubmed publisher
    ..Interestingly, β-arrestin2 can interact with the ARF guanine nucleotide exchange factor ARNO, although the C-terminally lacking mutant does not...
  14. Xu K, Gao J, Yang X, Yao Y, Liu Q. Cytohesin-2 as a novel prognostic marker for hepatocellular carcinoma. Oncol Rep. 2013;29:2211-8 pubmed publisher
    ..In conclusion, cytohesin-2 may identify low-and high-risk individuals with HCC and may be a valuable indicator for stratifying prognosis of TNM stage I patients. Cytohesin-2 may serve as a novel prognostic biomarker for HCC. ..
  15. Lee S, Wurtzel J, Goldfinger L. The RLIP76 N-terminus binds ARNO to regulate PI 3-kinase, Arf6 and Rac signaling, cell spreading and migration. Biochem Biophys Res Commun. 2014;454:560-5 pubmed publisher
    ..RLIP76 harbors docking sites for many proteins, and we have found that it interacts with ARNO, a guanine nucleotide exchange factor for Arf6, and that RLIP76 regulates activation of Rac1 via Arf6, and ..
  16. Bruno G, Pagano E, Rossi E, Cataudella S, De Rosa M, Marchesini G, et al. Incidence, prevalence, costs and quality of care of type 1 diabetes in Italy, age 0-29 years: The population-based CINECA-SID ARNO Observatory, 2002-2012. Nutr Metab Cardiovasc Dis. 2016;26:1104-1111 pubmed publisher
    ..The ARNO Observatory, a healthcare monitoring system based on administrative data, identified a population-based ..
  17. Lee S, Pohajdak B. N-terminal targeting of guanine nucleotide exchange factors (GEF) for ADP ribosylation factors (ARF) to the Golgi. J Cell Sci. 2000;113 ( Pt 11):1883-9 pubmed
    B2-1 (cytohesin-1) is a member of a group of proteins (including ARNO and ARNO3) that are all of similar size and domain composition...
  18. Wurtzel J, Lee S, Singhal S, Awasthi S, Ginsberg M, Goldfinger L. RLIP76 regulates Arf6-dependent cell spreading and migration by linking ARNO with activated R-Ras at recycling endosomes. Biochem Biophys Res Commun. 2015;467:785-91 pubmed publisher
    ..Here, we report that RLIP76 performs these functions by binding cytohesin-2/ARNO, an Arf GTPase guanine exchange factor, and connecting it to R-Ras at recycling endosomes...
  19. Guaraldi G, Zona S, Menozzi M, Brothers T, Carli F, Stentarelli C, et al. Late presentation increases risk and costs of non-infectious comorbidities in people with HIV: an Italian cost impact study. AIDS Res Ther. 2017;14:8 pubmed publisher
    ..HIV-positive participants were matched in a 1:3 ratio with HIV-negative participants from the CINECA ARNO database. Multimorbidity was defined as the concurrent presence of ?2 NICM...
  20. Yamaoka M, Ando T, Terabayashi T, Okamoto M, Takei M, Nishioka T, et al. PI3K regulates endocytosis after insulin secretion by mediating signaling crosstalk between Arf6 and Rab27a. J Cell Sci. 2016;129:637-49 pubmed publisher
    ..also known as TBC1D10A) and identified the Arf6 guanine-nucleotide-exchange factor (GEF) ARNO (also known as CYTH2) in pancreatic β-cells...
  21. Benabdi S, Peurois F, Nawrotek A, Chikireddy J, Cañeque T, Yamori T, et al. Family-wide Analysis of the Inhibition of Arf Guanine Nucleotide Exchange Factors with Small Molecules: Evidence of Unique Inhibitory Profiles. Biochemistry. 2017;56:5125-5133 pubmed publisher
    ..four structurally distinct ArfGEF inhibitors, Brefeldin A, SecinH3, M-COPA, and NAV-2729, toward six ArfGEFs (human ARNO, EFA6, BIG1, and BRAG2 and Legionella and Rickettsia RalF)...
  22. Maggioni A, Calabria S, Rossi E, Martini N. Use of lipid lowering drugs in patients at very high risk of cardiovascular events: An analysis on nearly 3,000,000 Italian subjects of the ARNO Observatory. Int J Cardiol. 2017;246:62-67 pubmed publisher
    ..was carried out of patient demographics, drug prescriptions, hospital discharge, specialty procedures from the ARNO Observatory, including 2,989,512 subjects of Local Health Units well representing the whole Italian country...
  23. Xie X, Tang S, Cai Y, Pi W, Deng L, Wu G, et al. Suppression of breast cancer metastasis through the inactivation of ADP-ribosylation factor 1. Oncotarget. 2016;7:58111-58120 pubmed publisher
    ..and LM11, a cell-active inhibitor that specifically inhibits ARF1 activation through targeting the ARF1-GDP/ARNO complex at the Golgi, significantly impairs metastatic capability of breast cancer cell in zebrafish...
  24. Dong W, Zhang G, Gao S. Preliminary in vitro analysis of mechanism of cardiac microvascular endothelial barrier function. Genet Mol Res. 2016;15: pubmed publisher
    ..However, IL-1? induced increase in vascular permeability, which nullified the function of cardiac microvascular endothelial barrier. These findings are closely related to the activation of the Arf6-VE-cadherin signaling pathway. ..
  25. Franssen E, Zhao R, Koseki H, Kanamarlapudi V, Hoogenraad C, Eva R, et al. Exclusion of integrins from CNS axons is regulated by Arf6 activation and the AIS. J Neurosci. 2015;35:8359-75 pubmed publisher
    ..of transport is controlled through the activation state of ARF6, with developmental upregulation of the ARF6 GEF ARNO enhancing retrograde transport...
  26. Merkulova M, Bakulina A, Thaker Y, Gruber G, Marshansky V. Specific motifs of the V-ATPase a2-subunit isoform interact with catalytic and regulatory domains of ARNO. Biochim Biophys Acta. 2010;1797:1398-409 pubmed publisher
    ..isoform interacts specifically, and in an intra-endosomal acidification-dependent manner, with the Arf-GEF ARNO. In the present study, we examined the molecular mechanism of this interaction using synthetic peptides and ..
  27. Hosokawa H, Dip P, Merkulova M, Bakulina A, Zhuang Z, Khatri A, et al. The N termini of a-subunit isoforms are involved in signaling between vacuolar H+-ATPase (V-ATPase) and cytohesin-2. J Biol Chem. 2013;288:5896-913 pubmed publisher
    ..Thus, here we have uncovered an evolutionarily conserved function of the V-ATPase as a novel cytohesin-signaling receptor. ..
  28. Renault L, Guibert B, Cherfils J. Structural snapshots of the mechanism and inhibition of a guanine nucleotide exchange factor. Nature. 2003;426:525-30 pubmed
    ..The structural characteristics of the reaction and its modes of inhibition reveal unexplored ways in which to inhibit the activation of small G proteins. ..
  29. Theis M, Knorre A, Kellersch B, Moelleken J, Wieland F, Kolanus W, et al. Discriminatory aptamer reveals serum response element transcription regulated by cytohesin-2. Proc Natl Acad Sci U S A. 2004;101:11221-6 pubmed
    ..Here, we selected and applied a specific inhibitor for ARF nucleotide-binding site opener (ARNO)/cytohesin-2, an RNA aptamer that clearly discriminates between cytohesin-1 and cytohesin-2...
  30. Anastasi S, Zhu S, Ballaro C, Manca S, Lamberti D, Wang L, et al. Lack of Evidence that CYTH2/ARNO Functions as a Direct Intracellular EGFR Activator. Cell. 2016;165:1031-1034 pubmed publisher
  31. Mossessova E, Gulbis J, Goldberg J. Structure of the guanine nucleotide exchange factor Sec7 domain of human arno and analysis of the interaction with ARF GTPase. Cell. 1998;92:415-23 pubmed
    ..Here we report the crystal structure of the catalytic Sec7 homology domain of Arno, a human GEF for ARF1, determined at 2.2 angstroms resolution...
  32. Buchet Poyau K, Mehenni H, Radhakrishna U, Antonarakis S. Search for the second Peutz-Jeghers syndrome locus: exclusion of the STK13, PRKCG, KLK10, and PSCD2 genes on chromosome 19 and the STK11IP gene on chromosome 2. Cytogenet Genome Res. 2002;97:171-8 pubmed
    ..Four genes in the region (cytohesin 2: PSCD2, kallikrein 10: KLK10, protein kinase C gamma: PRKCG, and serine/threonine kinase 13: STK13) potentially ..
  33. Pawar A, Meier J, Dasgupta A, Diwanji N, Deshpande N, Saxena K, et al. Ral-Arf6 crosstalk regulates Ral dependent exocyst trafficking and anchorage independent growth signalling. Cell Signal. 2016;28:1225-36 pubmed publisher
    ..Active Ral we further find uses a Ral-RalBP1-ARNO-Arf6 pathway to mediate Arf6 activation...
  34. Humphreys D, Singh V, Koronakis V. Inhibition of WAVE Regulatory Complex Activation by a Bacterial Virulence Effector Counteracts Pathogen Phagocytosis. Cell Rep. 2016;17:697-707 pubmed publisher
    ..polymerization mediated by the WAVE regulatory complex (WRC), small GTPases Arf and Rac1, and the Arf1 activator ARNO. To establish extracellular infections, enteropathogenic (EPEC) and enterohaemorrhagic (EHEC) Escherichia coli ..
  35. Kim H. Assignment of the human cts18.1 gene PSCD2L to chromosome 19 band q13 using a radiation hybrid mapping panel. Cytogenet Cell Genet. 1998;83:43 pubmed
  36. Zhu W, Shi D, Winter J, Rich B, Tong Z, Sorensen L, et al. Small GTPase ARF6 controls VEGFR2 trafficking and signaling in diabetic retinopathy. J Clin Invest. 2017;: pubmed publisher
    ..ARF6 activation was independently regulated by 2 different ARF GEFs - ARNO and GEP100...
  37. Srinivasaraghavan K, Nacro K, Gruber G, Verma C. Effect of Ser392 phosphorylation on the structure and dynamics of the polybasic domain of ADP ribosylation factor nucleotide site opener protein: a molecular simulation study. Biochemistry. 2013;52:7339-49 pubmed publisher
    ADP ribosylation factor nucleotide site opener (ARNO) as a guanine nucleotide exchange factor (GEF) activates small GTPases called ADP ribosylation factors (Arfs), which function as molecular switches and regulate a variety of cell ..
  38. Rafiq N, Lieu Z, Jiang T, Yu C, Matsudaira P, Jones G, et al. Podosome assembly is controlled by the GTPase ARF1 and its nucleotide exchange factor ARNO. J Cell Biol. 2017;216:181-197 pubmed publisher produce podosomes, down-regulation of the G-protein ARF1 or the ARF1 guanine nucleotide exchange factor, ARNO, by small, interfering RNA or pharmacological inhibitors led to striking podosome elimination...
  39. Salem J, Reviriego Mendoza M, Santy L. ARF-GEF cytohesin-2/ARNO regulates R-Ras and α5-integrin recycling through an EHD1-positive compartment. Mol Biol Cell. 2015;26:4265-79 pubmed publisher
    When expressed in epithelial cells, cytohesin-2/ARNO, a guanine nucleotide exchange factor (GEF) for ARF small GTPases, causes a robust migration response...
  40. Mohanan V, Nakata T, Desch A, Lévesque C, Boroughs A, Guzman G, et al. C1orf106 is a colitis risk gene that regulates stability of epithelial adherens junctions. Science. 2018;359:1161-1166 pubmed publisher
    ..These findings delineate a mechanism by which a genetic polymorphism fine-tunes intestinal epithelial barrier integrity and elucidate a fundamental mechanism of cellular junctional control. ..
  41. Gillingham A, Munro S. Identification of a guanine nucleotide exchange factor for Arf3, the yeast orthologue of mammalian Arf6. PLoS ONE. 2007;2:e842 pubmed
    ..Moreover the Sec7 domain of Yel1 is required for its membrane targeting and for that of Arf3. Finally we show that the isolated Yel1 Sec7 domain strongly stimulates nucleotide exchange activity specifically on Arf3 in vitro. ..
  42. Humphreys D, Davidson A, Hume P, Koronakis V. Salmonella virulence effector SopE and Host GEF ARNO cooperate to recruit and activate WAVE to trigger bacterial invasion. Cell Host Microbe. 2012;11:129-39 pubmed publisher
    ..Arf3 and Arf6 could also enhance invasion. RNAi screening of host Arf-family GEFs revealed a key role for ARNO in pathogen invasion and generation of pathogen-containing macropinosomes enriched in Arf1 and WRC...
  43. Gsandtner I, Charalambous C, Stefan E, Ogris E, Freissmuth M, Zezula J. Heterotrimeric G protein-independent signaling of a G protein-coupled receptor. Direct binding of ARNO/cytohesin-2 to the carboxyl terminus of the A2A adenosine receptor is necessary for sustained activation of the ERK/MAP kinase pathway. J Biol Chem. 2005;280:31898-905 pubmed
    ..This approach identified ARNO/cytohesin-2, a nucleotide exchange factor for the small (monomeric) G proteins of the Arf (ADP-ribosylation factor) ..
  44. Peurois F, Veyron S, Ferrandez Y, Ladid I, Benabdi S, Zeghouf M, et al. Characterization of the activation of small GTPases by their GEFs on membranes using artificial membrane tethering. Biochem J. 2017;474:1259-1272 pubmed publisher
    ..membranes and revealed that all isoforms are efficiently activated by two GEFs with different regulatory regimes, ARNO and Brag2...
  45. Li C, Chiang T, Wu T, Pacheco Rodriguez G, Moss J, Lee F. ARL4D recruits cytohesin-2/ARNO to modulate actin remodeling. Mol Biol Cell. 2007;18:4420-37 pubmed
    ..Cytohesin-2/ARF nucleotide-binding-site opener (ARNO) is a guanine nucleotide-exchange factor (GEF) for ARF, and, at the plasma membrane, it can activate ARF6 to ..
  46. Oh S, Santy L. Phosphoinositide specificity determines which cytohesins regulate ?1 integrin recycling. J Cell Sci. 2012;125:3195-201 pubmed publisher
    ..Recently, we determined that the ADP-ribosylation factor-guanine nucleotide exchange factors (ARF-GEFs) cytohesin 2/ARNO and cytohesin 3/GRP1 have opposing effects on adhesion and stimulated ?1 integrin recycling even though ..
  47. White D, McShea K, Attar M, Santy L. GRASP and IPCEF promote ARF-to-Rac signaling and cell migration by coordinating the association of ARNO/cytohesin 2 with Dock180. Mol Biol Cell. 2010;21:562-71 pubmed publisher
    ..ARNO/cytohesin 2 is an ARF-activating protein that promotes cell migration and cell shape changes...
  48. Claing A, Chen W, Miller W, Vitale N, Moss J, Premont R, et al. beta-Arrestin-mediated ADP-ribosylation factor 6 activation and beta 2-adrenergic receptor endocytosis. J Biol Chem. 2001;276:42509-13 pubmed the ability of the ARF GTPase-activating protein GIT1 to inhibit and of the ARF nucleotide exchange factor, ARNO, to enhance receptor endocytosis. Endogenous beta-arrestin is found in complex with ARNO...
  49. Yano H, Kobayashi I, Onodera Y, Luton F, Franco M, Mazaki Y, et al. Fbx8 makes Arf6 refractory to function via ubiquitination. Mol Biol Cell. 2008;19:822-32 pubmed
    ..Our results indicate that dysfunction of Fbx8 expression may contribute to the invasiveness of some breast cancer cells. ..
  50. Peyroche A, Antonny B, Robineau S, Acker J, Cherfils J, Jackson C. Brefeldin A acts to stabilize an abortive ARF-GDP-Sec7 domain protein complex: involvement of specific residues of the Sec7 domain. Mol Cell. 1999;3:275-85 pubmed
    ..for BFA inhibition of ARF exchange activity, since mutations in these residues of Gea1p (sensitive to BFA) and of ARNO (resistant to BFA) reverse the sensitivity of each to BFA in vivo and in vitro...
  51. Rouhana J, Padilla A, Estaran S, Bakari S, Delbecq S, Boublik Y, et al. Kinetics of interaction between ADP-ribosylation factor-1 (Arf1) and the Sec7 domain of Arno guanine nucleotide exchange factor, modulation by allosteric factors, and the uncompetitive inhibitor brefeldin A. J Biol Chem. 2013;288:4659-72 pubmed publisher
    The GDP/GTP nucleotide exchange of Arf1 is catalyzed by nucleotide exchange factors (GEF), such as Arno, which act through their catalytic Sec7 domain...
  52. Giguère P, Rochdi M, Laroche G, Dupré E, Whorton M, Sunahara R, et al. ARF6 activation by Galpha q signaling: Galpha q forms molecular complexes with ARNO and ARF6. Cell Signal. 2006;18:1988-94 pubmed
    ..Co-immunoprecipitation studies revealed that ARNO (a guanine nucleotide exchange factor for ARF6) and ARF6 formed complexes preferentially with activated Galpha(q) ..
  53. Cherfils J, Menetrey J, Mathieu M, Le Bras G, Robineau S, Beraud Dufour S, et al. Structure of the Sec7 domain of the Arf exchange factor ARNO. Nature. 1998;392:101-5 pubmed
    ..An exchange factor for human Arf1, ARNO, and two closely related proteins, named cytohesin 1 and GPS1, have been identified...
  54. Ellong E, Soni K, Bui Q, Sougrat R, Golinelli Cohen M, Jackson C. Interaction between the triglyceride lipase ATGL and the Arf1 activator GBF1. PLoS ONE. 2011;6:e21889 pubmed publisher
    ..We suggest that interaction of GBF1 with ATGL may be involved in the membrane trafficking pathway mediated by GBF1, Arf1 and COPI that contributes to the localization of ATGL to lipid droplets. ..
  55. Jayaram B, Kowluru A. Phagocytic NADPH oxidase links ARNO-Arf6 signaling pathway in glucose-stimulated insulin secretion from the pancreatic β-cell. Cell Physiol Biochem. 2012;30:1351-62 pubmed publisher
    ..g., Tiam1) and Arf6 (e.g., ARNO) in clonal INS-1 832/13 cells, normal rat islets and human islets...
  56. Torii T, Miyamoto Y, Sanbe A, Nishimura K, Yamauchi J, Tanoue A. Cytohesin-2/ARNO, through its interaction with focal adhesion adaptor protein paxillin, regulates preadipocyte migration via the downstream activation of Arf6. J Biol Chem. 2010;285:24270-81 pubmed publisher
  57. Laroche G, Giguère P, Dupré E, Dupuis G, Parent J. The N-terminal coiled-coil domain of the cytohesin/ARNO family of guanine nucleotide exchange factors interacts with Galphaq. Mol Cell Biochem. 2007;306:141-52 pubmed
    ..that Galphaq signaling leads to the activation of ARF6, possibly through a direct interaction with cytohesin-2/ARNO. Here, we report that Galphaq can directly interact with cytohesin-1, another Arf-GEF of the ARNO/cytohesin family...
  58. Garza Mayers A, Miller K, Russo B, Nagda D, Goldberg M. Shigella flexneri regulation of ARF6 activation during bacterial entry via an IpgD-mediated positive feedback loop. MBio. 2015;6:e02584 pubmed publisher
    ..The cytohesin GEF ARF nucleotide binding site opener (ARNO) is recruited to these sites, also dependent on IpgD phosphatase activity...
  59. Merkulova M, Hurtado Lorenzo A, Hosokawa H, Zhuang Z, Brown D, Ausiello D, et al. Aldolase directly interacts with ARNO and modulates cell morphology and acidic vesicle distribution. Am J Physiol Cell Physiol. 2011;300:C1442-55 pubmed publisher an endosomal pH sensor that interacts with the ADP-ribosylation factor (Arf) guanine nucleotide exchange factor, ARNO. In the present study, we showed that ARNO directly interacts not only with the a2-subunit but with all a-isoforms (..
  60. Viaud J, Zeghouf M, Barelli H, Zeeh J, Padilla A, Guibert B, et al. Structure-based discovery of an inhibitor of Arf activation by Sec7 domains through targeting of protein-protein complexes. Proc Natl Acad Sci U S A. 2007;104:10370-5 pubmed
    ..Arf1, a major regulator of membrane traffic, by the Sec7 catalytic domain of its guanine nucleotide exchange factor ARNO. The crystal structure of the Arf1-GDP/ARNO complex, which initiates the exchange reaction, was used to discover an ..
  61. Venkateswarlu K, Hanada T, Chishti A. Centaurin-alpha1 interacts directly with kinesin motor protein KIF13B. J Cell Sci. 2005;118:2471-84 pubmed
    ..Together, our data suggest a mechanism where direct binding between centaurin-alpha(1) and KIF13B could concentrate centaurin-alpha(1) at the leading edges of cells, thus modulating ARF6 function. ..
  62. Smith J, Tachibana I, Pohl U, Lee H, Thanarajasingam U, Portier B, et al. A transcript map of the chromosome 19q-arm glioma tumor suppressor region. Genomics. 2000;64:44-50 pubmed
    ..Tumor-specific alterations have not been identified in the transcripts examined thus far. Collectively, these data should facilitate subsequent efforts to identify and characterize the remaining transcripts in the 1.6-Mb interval. ..
  63. Miao B, Skidan I, Yang J, Lugovskoy A, Reibarkh M, Long K, et al. Small molecule inhibition of phosphatidylinositol-3,4,5-triphosphate (PIP3) binding to pleckstrin homology domains. Proc Natl Acad Sci U S A. 2010;107:20126-31 pubmed publisher
    ..Overall, our studies demonstrate the feasibility of developing specific small molecule antagonists of PIP3 signaling...
  64. Hurtado Lorenzo A, Skinner M, El Annan J, Futai M, Sun Wada G, Bourgoin S, et al. V-ATPase interacts with ARNO and Arf6 in early endosomes and regulates the protein degradative pathway. Nat Cell Biol. 2006;8:124-36 pubmed
    The recruitment of the small GTPase Arf6 and ARNO from cytosol to endosomal membranes is driven by V-ATPase-dependent intra-endosomal acidification...
  65. Kolanus W, Nagel W, Schiller B, Zeitlmann L, Godar S, Stockinger H, et al. Alpha L beta 2 integrin/LFA-1 binding to ICAM-1 induced by cytohesin-1, a cytoplasmic regulatory molecule. Cell. 1996;86:233-42 pubmed
    ..Similar inhibition is not exhibited by PH domains taken from other proteins, showing that the interaction is specific and that individual PH domains are capable of discriminating between alternative targets. ..
  66. Bouschet T, Martin S, Kanamarlapudi V, Mundell S, Henley J. The calcium-sensing receptor changes cell shape via a beta-arrestin-1 ARNO ARF6 ELMO protein network. J Cell Sci. 2007;120:2489-97 pubmed
    ..calcium, triggers plasma membrane (PM) ruffling via a pathway that involves beta-arrestin 1, Arf nucleotide binding site opener (ARNO), ADP-ribosylating factor 6 (ARF6) and engulfment and cell motility protein (ELMO)...
  67. Mannell H, Pircher J, Chaudhry D, Alig S, Koch E, Mettler R, et al. ARNO regulates VEGF-dependent tissue responses by stabilizing endothelial VEGFR-2 surface expression. Cardiovasc Res. 2012;93:111-9 pubmed publisher
    ..ADP-ribosylation factor (ARF) nucleotide-binding site opener (ARNO) (cytohesin-2) is a guanine exchange factor important for cellular signalling through ARF GTPases...
  68. Ogasawara M, Kim S, Adamik R, Togawa A, Ferrans V, Takeda K, et al. Similarities in function and gene structure of cytohesin-4 and cytohesin-1, guanine nucleotide-exchange proteins for ADP-ribosylation factors. J Biol Chem. 2000;275:3221-30 pubmed
    ..Thus, in gene structure and brefeldin A-insensitive GEP activity, cytohesin-4 resembles other cytohesins, but its tissue distribution differs considerably, consistent with a different specific function. ..
  69. van den Bosch M, Poole A, Hers I. Cytohesin-2 phosphorylation by protein kinase C relieves the constitutive suppression of platelet dense granule secretion by ADP-ribosylation factor 6. J Thromb Haemost. 2014;12:726-35 pubmed publisher
    ..PKC-mediated phosphorylation of cytohesin-2 relieves this inhibitory effect, thereby promoting platelet secretion and aggregation. ..
  70. Torii T, Miyamoto Y, Nakamura K, Maeda M, Yamauchi J, Tanoue A. Arf6 guanine-nucleotide exchange factor, cytohesin-2, interacts with actinin-1 to regulate neurite extension. Cell Signal. 2012;24:1872-82 pubmed publisher
    ..Here, we show that the Arf6 guanine-nucleotide exchange factor (GEF), cytohesin-2 (CYTH2), interacts with the cytoskeletal protein actinin-1 (ACTN1) and regulates neurite extension in N1E-115 cells used ..
  71. Huh M, Han J, Lim C, Lee S, Kim S, Kim E, et al. Regulation of neuritogenesis and synaptic transmission by msec7-1, a guanine nucleotide exchange factor, in cultured Aplysia neurons. J Neurochem. 2003;85:282-5 pubmed
    ..Similarly, the overexpression of ARNO, another mammalin GEF, produces extensive neuritogenesis in Aplysia neurons...
  72. Vitale N, Pacheco Rodriguez G, Ferrans V, Riemenschneider W, Moss J, Vaughan M. Specific functional interaction of human cytohesin-1 and ADP-ribosylation factor domain protein (ARD1). J Biol Chem. 2000;275:21331-9 pubmed
    ..It was concluded that cytohesin-1 is likely to be involved in ARD1 activation, consistent with a role for ARD1 in the regulation of vesicular trafficking. ..
  73. Pan T, Sun J, Hu J, Hu Y, Zhou J, Chen Z, et al. Cytohesins/ARNO: the function in colorectal cancer cells. PLoS ONE. 2014;9:e90997 pubmed publisher
    ..This study found that ARNO (cytohesin-2), an activator of the EGF and IGF-I pathways, was more highly expressed in colorectal cancer tissue ..