Skip to main content
SpringerLink
Log in

Signaling network map of the aryl hydrocarbon receptor

  • Nuts and Bolts
  • Published:
Journal of Cell Communication and Signaling Aims and scope

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Abbreviations

AHR:

Aryl Hydrocarbon Receptor

TCDD:

2,3,7,8-tetrachlorodibenzo-p-dioxin

PPI:

Protein-protein interaction

PTM:

Post-translational modification

HPRD:

Human Protein Reference Database

SBML:

Systems Biology Markup Language

PSI-MI:

Proteomics Standards Initiative for Molecular Interaction

BioPAX:

Biological Pathway Exchange

References

  • Abel J, Haarmann-Stemmann T (2010) An introduction to the molecular basics of aryl hydrocarbon receptor biology. Biol Chem 391:1235–1248

    Article  CAS  PubMed  Google Scholar 

  • Boeckmann B, Bairoch A, Apweiler R, Blatter MC, Estreicher A, Gasteiger E, Martin MJ, Michoud K, O’Donovan C, Phan I, Pilbout S, Schneider M (2003) The SWISS-PROT protein knowledgebase and its supplement TrEMBL in 2003. Nucleic Acids Res 31:365–370

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen K, Pociask DA, McAleer JP, Chan YR, Alcorn JF, Kreindler JL, Keyser MR, Shapiro SD, Houghton AM, Kolls JK, Zheng M (2011) IL-17RA is required for CCL2 expression, macrophage recruitment, and emphysema in response to cigarette smoke. PLoS One 6:e20333

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cheng YH, Huang SC, Lin CJ, Cheng LC, Li LA (2012) Aryl hydrocarbon receptor protects lung adenocarcinoma cells against cigarette sidestream smoke particulates-induced oxidative stress. Toxicol Appl Pharmacol 259:293–301

    Article  CAS  PubMed  Google Scholar 

  • Demir E, Cary MP, Paley S, Fukuda K, Lemer C, Vastrik I, Wu G, D’Eustachio P, Schaefer C, Luciano J, Schacherer F, Martinez-Flores I, Hu Z, Jimenez-Jacinto V, Joshi-Tope G, Kandasamy K, Lopez-Fuentes AC, Mi H, Pichler E, Rodchenkov I, Splendiani A, Tkachev S, Zucker J, Gopinath G, Rajasimha H, Ramakrishnan R, Shah I, Syed M, Anwar N, Babur O, Blinov M, Brauner E, Corwin D, Donaldson S, Gibbons F, Goldberg R, Hornbeck P, Luna A, Murray-Rust P, Neumann E, Ruebenacker O, Samwald M, van Iersel M, Wimalaratne S, Allen K, Braun B, Whirl-Carrillo M, Cheung KH, Dahlquist K, Finney A, Gillespie M, Glass E, Gong L, Haw R, Honig M, Hubaut O, Kane D, Krupa S, Kutmon M, Leonard J, Marks D, Merberg D, Petri V, Pico A, Ravenscroft D, Ren L, Shah N, Sunshine M, Tang R, Whaley R, Letovksy S, Buetow KH, Rzhetsky A, Schachter V, Sobral BS, Dogrusoz U, McWeeney S, Aladjem M, Birney E, Collado-Vides J, Goto S, Hucka M, Le Novere N, Maltsev N, Pandey A, Thomas P, Wingender E, Karp PD, Sander C, Bader GD (2010) The BioPAX community standard for pathway data sharing. Nat Biotechnol 28:935–942

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dever DP, Opanashuk LA (2012) The aryl hydrocarbon receptor contributes to the proliferation of human medulloblastoma cells. Mol Pharmacol 81:669–678

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hall JM, Barhoover MA, Kazmin D, McDonnell DP, Greenlee WF, Thomas RS (2010) Activation of the aryl-hydrocarbon receptor inhibits invasive and metastatic features of human breast cancer cells and promotes breast cancer cell differentiation. Mol Endocrinol 24:359–369

    Article  CAS  PubMed  Google Scholar 

  • Hamosh A, Scott AF, Amberger JS, Bocchini CA, McKusick VA (2005) Online Mendelian inheritance in man (OMIM), a knowledgebase of human genes and genetic disorders. Nucleic Acids Res 33:D514–D517

    Article  CAS  PubMed  Google Scholar 

  • Hansen DA, Esakky P, Drury A, Lamb L, Moley KH (2014) The aryl hydrocarbon receptor is important for proper seminiferous tubule architecture and sperm development in mice. Biol Reprod 90:8

    Article  PubMed  Google Scholar 

  • Heliovaara E, Raitila A, Launonen V, Paetau A, Arola J, Lehtonen H, Sane T, Weil RJ, Vierimaa O, Salmela P, Tuppurainen K, Makinen M, Aaltonen LA, Karhu A (2009) The expression of AIP-related molecules in elucidation of cellular pathways in pituitary adenomas. Am J Pathol 175:2501–2507

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hermjakob H, Montecchi-Palazzi L, Bader G, Wojcik J, Salwinski L, Ceol A, Moore S, Orchard S, Sarkans U, von Mering C, Roechert B, Poux S, Jung E, Mersch H, Kersey P, Lappe M, Li Y, Zeng R, Rana D, Nikolski M, Husi H, Brun C, Shanker K, Grant SG, Sander C, Bork P, Zhu W, Pandey A, Brazma A, Jacq B, Vidal M, Sherman D, Legrain P, Cesareni G, Xenarios I, Eisenberg D, Steipe B, Hogue C, Apweiler R (2004) The HUPO PSI’s molecular interaction format--a community standard for the representation of protein interaction data. Nat Biotechnol 22:177–183

    Article  CAS  PubMed  Google Scholar 

  • Hsieh TH, Tsai CF, Hsu CY, Kuo PL, Lee JN, Chai CY, Wang SC, Tsai EM (2012) Phthalates induce proliferation and invasiveness of estrogen receptor-negative breast cancer through the AhR/HDAC6/c-Myc signaling pathway. FASEB J 26:778–787

    Article  CAS  PubMed  Google Scholar 

  • Hucka M, Finney A, Sauro HM, Bolouri H, Doyle JC, Kitano H, Arkin AP, Bornstein BJ, Bray D, Cornish-Bowden A, Cuellar AA, Dronov S, Gilles ED, Ginkel M, Gor V, Goryanin II, Hedley WJ, Hodgman TC, Hofmeyr JH, Hunter PJ, Juty NS, Kasberger JL, Kremling A, Kummer U, Le Novere N, Loew LM, Lucio D, Mendes P, Minch E, Mjolsness ED, Nakayama Y, Nelson MR, Nielsen PF, Sakurada T, Schaff JC, Shapiro BE, Shimizu TS, Spence HD, Stelling J, Takahashi K, Tomita M, Wagner J, Wang J (2003) The systems biology markup language (SBML): a medium for representation and exchange of biochemical network models. Bioinformatics 19:524–531

    Article  CAS  PubMed  Google Scholar 

  • Jaffrain-Rea ML, Angelini M, Gargano D, Tichomirowa MA, Daly AF, Vanbellinghen JF, D’Innocenzo E, Barlier A, Giangaspero F, Esposito V, Ventura L, Arcella A, Theodoropoulou M, Naves LA, Fajardo C, Zacharieva S, Rohmer V, Brue T, Gulino A, Cantore G, Alesse E, Beckers A (2009) Expression of aryl hydrocarbon receptor (AHR) and AHR-interacting protein in pituitary adenomas: pathological and clinical implications. Endocr Relat Cancer 16:1029–1043

    Article  CAS  PubMed  Google Scholar 

  • Kadow S, Jux B, Zahner SP, Wingerath B, Chmill S, Clausen BE, Hengstler J, Esser C (2011) Aryl hydrocarbon receptor is critical for homeostasis of invariant gammadelta T cells in the murine epidermis. J Immunol 187:3104–3110

    Article  CAS  PubMed  Google Scholar 

  • Kandasamy K, Keerthikumar S, Raju R, Keshava Prasad TS, Ramachandra YL, Mohan S, Pandey A (2009) PathBuilder--open source software for annotating and developing pathway resources. Bioinformatics 25:2860–2862

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kandasamy K, Mohan SS, Raju R, Keerthikumar S, Kumar GS, Venugopal AK, Telikicherla D, Navarro JD, Mathivanan S, Pecquet C, Gollapudi SK, Tattikota SG, Mohan S, Padhukasahasram H, Subbannayya Y, Goel R, Jacob HK, Zhong J, Sekhar R, Nanjappa V, Balakrishnan L, Subbaiah R, Ramachandra YL, Rahiman BA, Prasad TS, Lin JX, Houtman JC, Desiderio S, Renauld JC, Constantinescu SN, Ohara O, Hirano T, Kubo M, Singh S, Khatri P, Draghici S, Bader GD, Sander C, Leonard WJ, Pandey A (2010) NetPath: a public resource of curated signal transduction pathways. Genome Biol 11:R3

    Article  PubMed  PubMed Central  Google Scholar 

  • Kerley-Hamilton JS, Trask HW, Ridley CJ, Dufour E, Lesseur C, Ringelberg CS, Moodie KL, Shipman SL, Korc M, Gui J, Shworak NW, Tomlinson CR (2012) Inherent and benzo[a]pyrene-induced differential aryl hydrocarbon receptor signaling greatly affects life span, atherosclerosis, cardiac gene expression, and body and heart growth in mice. Toxicol Sci 126:391–404

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kewley RJ, Whitelaw ML, Chapman-Smith A (2004) The mammalian basic helix-loop-helix/PAS family of transcriptional regulators. Int J Biochem Cell Biol 36:189–204

    Article  CAS  PubMed  Google Scholar 

  • Koliopanos A, Kleeff J, Xiao Y, Safe S, Zimmermann A, Buchler MW, Friess H (2002) Increased arylhydrocarbon receptor expression offers a potential therapeutic target for pancreatic cancer. Oncogene 21:6059–6070

    Article  CAS  PubMed  Google Scholar 

  • Lees MJ, Peet DJ, Whitelaw ML (2003) Defining the role for XAP2 in stabilization of the dioxin receptor. J Biol Chem 278:35878–35888

    Article  CAS  PubMed  Google Scholar 

  • Lindsey S, Papoutsakis ET (2012) The evolving role of the aryl hydrocarbon receptor (AHR) in the normophysiology of hematopoiesis. Stem Cell Rev 8:1223–1235

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maglott D, Ostell J, Pruitt KD, Tatusova T (2011) Entrez Gene: gene-centered information at NCBI. Nucleic Acids Res 39:D52–D57

    Article  CAS  PubMed  Google Scholar 

  • Marconett CN, Sundar SN, Poindexter KM, Stueve TR, Bjeldanes LF, Firestone GL (2010) Indole-3-carbinol triggers aryl hydrocarbon receptor-dependent estrogen receptor (ER)alpha protein degradation in breast cancer cells disrupting an ERalpha-GATA3 transcriptional cross-regulatory loop. Mol Biol Cell 21:1166–1177

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Martey CA, Baglole CJ, Gasiewicz TA, Sime PJ, Phipps RP (2005) The aryl hydrocarbon receptor is a regulator of cigarette smoke induction of the cyclooxygenase and prostaglandin pathways in human lung fibroblasts. Am J Phys Lung Cell Mol Phys 289:L391–L399

    CAS  Google Scholar 

  • Matthews J, Wihlen B, Thomsen J, Gustafsson JA (2005) Aryl hydrocarbon receptor-mediated transcription: ligand-dependent recruitment of estrogen receptor alpha to 2,3,7,8-tetrachlorodibenzo-p-dioxin-responsive promoters. Mol Cell Biol 25:5317–5328

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Morgan RM, Hernandez-Ramirez LC, Trivellin G, Zhou L, Roe SM, Korbonits M, Prodromou C (2012) Structure of the TPR domain of AIP: lack of client protein interaction with the C-terminal alpha-7 helix of the TPR domain of AIP is sufficient for pituitary adenoma predisposition. PLoS One 7:e53339

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Murray IA, Patterson AD, Perdew GH (2014) Aryl hydrocarbon receptor ligands in cancer: friend and foe. Nat Rev Cancer 14:801–814

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nanjappa V, Raju R, Muthusamy B, Sharma J, Thomas JK, Nidhina PAH, Harsha HC, Pandey A, Anilkumar G, Prasad TSK (2011) A comprehensive curated reaction map of leptin signaling pathway. J Proteome Bioinf 4:184–189

    Google Scholar 

  • Nguyen LP, Bradfield CA (2008) The search for endogenous activators of the aryl hydrocarbon receptor. Chem Res Toxicol 21:102–116

    Article  CAS  PubMed  Google Scholar 

  • Noda S, Harada N, Hida A, Fujii-Kuriyama Y, Motohashi H, Yamamoto M (2003) Gene expression of detoxifying enzymes in AhR and Nrf2 compound null mutant mouse. Biochem Biophys Res Commun 303:105–111

    Article  CAS  PubMed  Google Scholar 

  • Ovrevik J, Lag M, Lecureur V, Gilot D, Lagadic-Gossmann D, Refsnes M, Schwarze PE, Skuland T, Becher R, Holme JA (2014) AhR and Arnt differentially regulate NF-kappaB signaling and chemokine responses in human bronchial epithelial cells. Cell Commun Signals 12:48

    Article  Google Scholar 

  • Peng TL, Chen J, Mao W, Liu X, Tao Y, Chen LZ, Chen MH (2009) Potential therapeutic significance of increased expression of aryl hydrocarbon receptor in human gastric cancer. World J Gastroenterol 15:1719–1729

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Podechard N, Lecureur V, Le Ferrec E, Guenon I, Sparfel L, Gilot D, Gordon JR, Lagente V, Fardel O (2008) Interleukin-8 induction by the environmental contaminant benzo(a)pyrene is aryl hydrocarbon receptor-dependent and leads to lung inflammation. Toxicol Lett 177:130–137

    Article  CAS  PubMed  Google Scholar 

  • Prasad TSK, Goel R, Kandasamy K, Keerthikumar S, Kumar S, Mathivanan S, Telikicherla D, Raju R, Shafreen B, Venugopal A, Balakrishnan L, Marimuthu A, Banerjee S, Somanathan DS, Sebastian A, Rani S, Ray S, Harrys Kishore CJ, Kanth S, Ahmed M, Kashyap MK, Mohmood R, Ramachandra YL, Krishna V, Rahiman BA, Mohan S, Ranganathan P, Ramabadran S, Chaerkady R, Pandey A (2009) Human protein reference database--2009 update. Nucleic Acids Res 37:D767–D772

    Article  CAS  Google Scholar 

  • Radhakrishnan A, Raju R, Tuladhar N, Subbannayya T, Thomas JK, Goel R, Telikicherla D, Palapetta SM, Rahiman BA, Venkatesh DD, Urmila KK, Harsha HC, Mathur PP, Prasad TS, Pandey A, Shemanko C, Chatterjee A (2012) A pathway map of prolactin signaling. J Cell Commun Signals 6:169–173

    Article  Google Scholar 

  • Raitila A, Lehtonen HJ, Arola J, Heliovaara E, Ahlsten M, Georgitsi M, Jalanko A, Paetau A, Aaltonen LA, Karhu A (2010) Mice with inactivation of aryl hydrocarbon receptor-interacting protein (Aip) display complete penetrance of pituitary adenomas with aberrant ARNT expression. Am J Pathol 177:1969–1976

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ramadoss P, Petrulis JR, Hollingshead BD, Kusnadi A, Perdew GH (2004) Divergent roles of hepatitis B virus X-associated protein 2 (XAP2) in human versus mouse ah receptor complexes. Biochemistry 43:700–709

    Article  CAS  PubMed  Google Scholar 

  • Savouret JF, Berdeaux A, Casper RF (2003) The aryl hydrocarbon receptor and its xenobiotic ligands: a fundamental trigger for cardiovascular diseases. Nutr Metab Cardiovasc Dis 13:104–113

    Article  CAS  PubMed  Google Scholar 

  • Trivellin G, Korbonits M (2011) AIP and its interacting partners. J Endocrinol 210:137–155

    Article  CAS  PubMed  Google Scholar 

  • Tsay JJ, Tchou-Wong KM, Greenberg AK, Pass H, Rom WN (2013) Aryl hydrocarbon receptor and lung cancer. Anticancer Res 33:1247–1256

    PubMed  PubMed Central  Google Scholar 

  • Tsuji N, Fukuda K, Nagata Y, Okada H, Haga A, Hatakeyama S, Yoshida S, Okamoto T, Hosaka M, Sekine K, Ohtaka K, Yamamoto S, Otaka M, Grave E, Itoh H (2014) The activation mechanism of the aryl hydrocarbon receptor (AhR) by molecular chaperone HSP90. FEBS Open Bio 4:796–803

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • van Iersel MP, Kelder T, Pico AR, Hanspers K, Coort S, Conklin BR, Evelo C (2008) Presenting and exploring biological pathways with PathVisio. BMC Bioinf 9:399

    Article  Google Scholar 

  • Veldhoen M, Hirota K, Westendorf AM, Buer J, Dumoutier L, Renauld JC, Stockinger B (2008) The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins. Nature 453:106–109

    Article  CAS  PubMed  Google Scholar 

  • Wang L, He X, Szklarz GD, Bi Y, Rojanasakul Y, Ma Q (2013) The aryl hydrocarbon receptor interacts with nuclear factor erythroid 2-related factor 2 to mediate induction of NAD(P)H:quinoneoxidoreductase 1 by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Arch Biochem Biophys 537:31–38

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Watabe Y, Nazuka N, Tezuka M, Shimba S (2010) Aryl hydrocarbon receptor functions as a potent coactivator of E2F1-dependent trascription activity. Biol Pharm Bull 33:389–397

    Article  CAS  PubMed  Google Scholar 

  • Xu C, Li CY, Kong AN (2005) Induction of phase I, II and III drug metabolism/transport by xenobiotics. Arch Pharm Res 28:249–268

    Article  CAS  PubMed  Google Scholar 

  • Zhang S, Qin C, Safe SH (2003) Flavonoids as aryl hydrocarbon receptor agonists/antagonists: effects of structure and cell context. Environ Health Perspect 111:1877–1882

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

We thank the Department of Biotechnology (DBT), Government of India for research support to the Institute of Bioinformatics, Bangalore. We thank the “Infosys Foundation” for research support to the Institute of Bioinformatics. We thank UK India Education and Research Initiative (UKIERI) for generous grant support. SDY is a recipient of DST-INSPIRE Senior Research Fellowship from Department of Science and Technology (DST), Government of India. AR and JA are recipients of Senior Research Fellowship from Council of Scientific and Industrial Research (CSIR), Government of India. RR is a recipient of Research Associateship from Department of Biotechnology, Government of India.

Author information

Authors and Affiliations

  1. Institute of Bioinformatics, International Technology Park, Whitefield, Bangalore, 560 066, India

    Soujanya D. Yelamanchi, Hitendra Singh Solanki, Aneesha Radhakrishnan, Lavanya Balakrishnan, Jayshree Advani, Remya Raja, Nandini A. Sahasrabuddhe, T. S. Keshava Prasad, Aditi Chatterjee & Harsha Gowda

  2. School of Biotechnology, KIIT University, Bhubaneswar, 751 024, India

    Soujanya D. Yelamanchi, Hitendra Singh Solanki & Premendu Prakash Mathur

  3. Department of Biochemistry and Molecular Biology, Pondicherry University, Puducherry, 605 014, India

    Aneesha Radhakrishnan & Premendu Prakash Mathur

  4. Manipal University, Madhav Nagar, Manipal, 576 104, India

    Jayshree Advani & T. S. Keshava Prasad

  5. Department of Endocrinology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India

    Pinaki Dutta

  6. NIMHANS-IOB Proteomics and Bioinformatics Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences, Bangalore, 560 029, India

    T. S. Keshava Prasad

  7. YU-IOB Center for Systems Biology and Molecular Medicine, Yenepoya University, Mangalore, 575 018, India

    T. S. Keshava Prasad, Aditi Chatterjee & Harsha Gowda

  8. Department of Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London, EC1A 6BQ, UK

    Márta Korbonits

  9. Department of Neurosurgery, Post Graduate Institute of Medical Education and Research, 5th Floor, F Block, Nehru Hospital, Chandigarh, 160 012, India

    Kanchan Kumar Mukherjee

Authors
  1. Soujanya D. Yelamanchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hitendra Singh Solanki
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Aneesha Radhakrishnan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lavanya Balakrishnan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jayshree Advani
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Remya Raja
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Nandini A. Sahasrabuddhe
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Premendu Prakash Mathur
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Pinaki Dutta
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. T. S. Keshava Prasad
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Márta Korbonits
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Aditi Chatterjee
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Harsha Gowda
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Kanchan Kumar Mukherjee
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Aditi Chatterjee, Harsha Gowda or Kanchan Kumar Mukherjee.

Ethics declarations

Conflict of interest

No potential conflicts of interest were declared.

Additional information

Soujanya D. Yelamanchi; Hitendra Singh Solanki and Aneesha Radhakrishnan contributed equally

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yelamanchi, S.D., Solanki, H.S., Radhakrishnan, A. et al. Signaling network map of the aryl hydrocarbon receptor. J. Cell Commun. Signal. 10, 341–346 (2016). https://doi.org/10.1007/s12079-016-0341-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12079-016-0341-y

Keywords

Search

Navigation