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Pathway Description

Ahr Signal Transduction Pathway

Rattus norvegicus

Category:

Protein Pathway

Sub-Categories:

Gene Regulatory

Cellular Response

Created: 2018-08-31

Last Updated: 2019-08-16

The aryl hydrocarbon receptor, known as AHR, is a normally cytosolic transcription factor that can bind to foreign compounds such as flavonoids and indoles from foods, as well as synthetic ligands including polychlorobiphenyls (PCBs) and polychlorinated dibenzo-p-dioxins (PCDD). This includes 2,3,7,8-tetrachlorodibenzodioxin (TCDD), which is the ligand shown in this pathway. AHR interacts with heat shock protein 90 (HSP90AA1), which acts as a chaperone for it. After this association, the ligand, in this case TCDD, can form a covalent bond with the complex in the cell's cytoplasm. This binding causes AHR and the rest of the complex to translocate into the nucleus of the cell. Once in the nucleus, the heat shock protein dissociates, leaving binding sites which the AHR nuclear translocator (ARNT) then binds to. Finally, the AHR/ARNT complex can interact, either directly or indirectly, with the DNA, in this case specifically a dioxin response element. With other ligands, the complex will bind to the equivalent DNA that corresponds to the genes that allow metabolism of the ligand.

References

Ahr Signal Transduction Pathway References

Carver LA, Hogenesch JB, Bradfield CA: Tissue specific expression of the rat Ah-receptor and ARNT mRNAs. Nucleic Acids Res. 1994 Aug 11;22(15):3038-44. doi: 10.1093/nar/22.15.3038.

Pubmed: 8065918

Elferink CJ, Whitlock JP Jr: Dioxin-dependent, DNA sequence-specific binding of a multiprotein complex containing the Ah receptor. Receptor. 1994 Fall;4(3):157-73.

Pubmed: 7812217

Pohjanvirta R, Wong JM, Li W, Harper PA, Tuomisto J, Okey AB: Point mutation in intron sequence causes altered carboxyl-terminal structure in the aryl hydrocarbon receptor of the most 2,3,7,8-tetrachlorodibenzo-p-dioxin-resistant rat strain. Mol Pharmacol. 1998 Jul;54(1):86-93. doi: 10.1124/mol.54.1.86.

Pubmed: 9658193

Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. doi: 10.1101/gr.2596504.

Pubmed: 15489334

Langer T, Fasold H: Isolation and quantification of the heat shock protein 90 alpha and beta isoforms from rat liver. Protoplasma. 2001;218(1-2):54-6.

Pubmed: 11732320

Liou ST, Wang C: Small glutamine-rich tetratricopeptide repeat-containing protein is composed of three structural units with distinct functions. Arch Biochem Biophys. 2005 Mar 15;435(2):253-63. doi: 10.1016/j.abb.2004.12.020.

Pubmed: 15708368

This pathway was propagated using PathWhiz - Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.

Propagated from SMP0063771

Highlighted elements will appear in red.

Highlight Compounds

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

Highlight Proteins

	Aryl hydrocarbon receptor
	Aryl hydrocarbon receptor nuclear translocator
	Heat shock protein HSP 90-alpha

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Visualize Compound Data

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

Visualize Protein Data