Pathways Knowlegdes

Biological pathway database

Pathway DOIs Note
Visual phototransduction

Accession ID: Reactome:R-CFA-2187338
  • 10.1002/neu.20242
  • 10.1016/0005-2728(93)90038-h
  • 10.1016/j.preteyeres.2010.11.001
  • 10.1016/j.preteyeres.2012.05.002
  • 10.1016/j.tibs.2010.01.005
  • 10.1074/jbc.r111.303008
  • 10.1074/jbc.r111.303990
  • 10.1093/jn/131.5.1405
  • 10.1111/j.1753-4887.2004.tb00053.x
  • 10.1146/annurev.nutr.25.050304.092614
  • 10.1152/physiol.00001.2010
  • 10.3390/nu3010063
 Korenbrot JI. Speed, sensitivity, and stability of the light response in rod and cone photoreceptors: Facts and models. Progress in Retinal and Eye Research. 2012 Sep;31(5):442–66. doi: 10.1016/j.preteyeres.2012.05.002.; von Lintig J. Metabolism of Carotenoids and Retinoids Related to Vision. Journal of Biological Chemistry. 2012 Jan;287(3):1627–34. doi: 10.1074/jbc.r111.303990.; Kefalov VJ. Rod and Cone Visual Pigments and Phototransduction through Pharmacological, Genetic, and Physiological Approaches. Journal of Biological Chemistry. 2012 Jan;287(3):1635–41. doi: 10.1074/jbc.r111.303008.; Wang J, Kefalov VJ. The Cone-specific visual cycle. Progress in Retinal and Eye Research. 2011 Mar;30(2):115–28. doi: 10.1016/j.preteyeres.2010.11.001.; D'Ambrosio DN, Clugston RD, Blaner WS. Vitamin A metabolism: an update. Nutrients. 2011 Jan;3(1):63–103. PMID: 21350678; PMCID: PMC3042718.; von Lintig J, Kiser PD, Golczak M, Palczewski K. The biochemical and structural basis for trans-to-cis isomerization of retinoids in the chemistry of vision. Trends in Biochemical Sciences. 2010 Jul;35(7):400–10. doi: 10.1016/j.tibs.2010.01.005.; Burns ME, Pugh EN. Lessons from photoreceptors: turning off g-protein signaling in living cells. Physiology (Bethesda). 2010 Apr;25(2):72–84. PMID: 20430952; PMCID: PMC2880230.; Blomhoff R, Blomhoff HK. Overview of retinoid metabolism and function. J Neurobiol. 2006 Jun;66(7):606–30. doi: 10.1002/neu.20242. PMID: 16688755.; Harrison EH. Mechanisms of digestion and absorption of dietary vitamin A. Annu Rev Nutr. 2005;25():87–103. doi: 10.1146/annurev.nutr.25.050304.092614. PMID: 16011460.; Wolf G. The visual cycle of the cone photoreceptors of the retina. Nutr Rev. 2004 Jul;62(7 Pt 1):283–6. doi: 10.1111/j.1753-4887.2004.tb00053.x. PMID: 15384919.; Harrison EH, Hussain MM. Mechanisms Involved in the Intestinal Digestion and Absorption of Dietary Vitamin A. The Journal of Nutrition. 2001 May;131(5):1405–8. doi: 10.1093/jn/131.5.1405.; Pugh EN, Lamb TD. Amplification and kinetics of the activation steps in phototransduction. Biochimica et Biophysica Acta (BBA) - Bioenergetics. 1993 Mar;1141(2-3):111–49. doi: 10.1016/0005-2728(93)90038-h.
Signaling by Retinoic Acid

Accession ID: Reactome:R-CFA-5362517
  • 10.1016/j.bbalip.2011.05.004
  • 10.1016/j.bbalip.2011.06.002
  • 10.1016/j.bmc.2013.11.025
  • 10.1146/annurev-nutr-072610-145127
 Das BC, Thapa P, Karki R, Das S, Mahapatra S, Liu T, Torregroza I, Wallace DP, Kambhampati S, Van Veldhuizen P, Verma A, Ray SK, Evans T. Retinoic acid signaling pathways in development and diseases. Bioorganic & Medicinal Chemistry. 2014 Jan;22(2):673–83. doi: 10.1016/j.bmc.2013.11.025.; Harrison EH. Mechanisms involved in the intestinal absorption of dietary vitamin A and provitamin A carotenoids. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 2012 Jan;1821(1):70–7. doi: 10.1016/j.bbalip.2011.06.002.; Napoli JL. Physiological insights into all-trans-retinoic acid biosynthesis. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 2012 Jan;1821(1):152–67. doi: 10.1016/j.bbalip.2011.05.004.; Catharine Ross A, Zolfaghari R. Cytochrome P450s in the Regulation of Cellular Retinoic Acid Metabolism. Annu. Rev. Nutr. 2011 Aug 21;31(1):65–87. doi: 10.1146/annurev-nutr-072610-145127.
The retinoid cycle in cones (daylight vision)

Accession ID: Reactome:R-DRE-2187335
  • 10.1016/j.preteyeres.2010.11.001
  • 10.1074/jbc.r111.303008
  • 10.1074/jbc.r111.303990
  • 10.1111/j.1753-4887.2004.tb00053.x
 von Lintig J. Metabolism of Carotenoids and Retinoids Related to Vision. Journal of Biological Chemistry. 2012 Jan;287(3):1627–34. doi: 10.1074/jbc.r111.303990.; Kefalov VJ. Rod and Cone Visual Pigments and Phototransduction through Pharmacological, Genetic, and Physiological Approaches. Journal of Biological Chemistry. 2012 Jan;287(3):1635–41. doi: 10.1074/jbc.r111.303008.; Wang J, Kefalov VJ. The Cone-specific visual cycle. Progress in Retinal and Eye Research. 2011 Mar;30(2):115–28. doi: 10.1016/j.preteyeres.2010.11.001.; Wolf G. The visual cycle of the cone photoreceptors of the retina. Nutr Rev. 2004 Jul;62(7 Pt 1):283–6. doi: 10.1111/j.1753-4887.2004.tb00053.x. PMID: 15384919.
RA biosynthesis pathway

Accession ID: Reactome:R-DRE-5365859
  • 10.1016/j.bbalip.2011.05.004
  • 10.1016/j.bmc.2013.11.025
 Das BC, Thapa P, Karki R, Das S, Mahapatra S, Liu T, Torregroza I, Wallace DP, Kambhampati S, Van Veldhuizen P, Verma A, Ray SK, Evans T. Retinoic acid signaling pathways in development and diseases. Bioorganic & Medicinal Chemistry. 2014 Jan;22(2):673–83. doi: 10.1016/j.bmc.2013.11.025.; Napoli JL. Physiological insights into all-trans-retinoic acid biosynthesis. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 2012 Jan;1821(1):152–67. doi: 10.1016/j.bbalip.2011.05.004.
Visual phototransduction

Accession ID: Reactome:R-DDI-2187338
  • 10.1002/neu.20242
  • 10.1016/0005-2728(93)90038-h
  • 10.1016/j.preteyeres.2010.11.001
  • 10.1016/j.preteyeres.2012.05.002
  • 10.1016/j.tibs.2010.01.005
  • 10.1074/jbc.r111.303008
  • 10.1074/jbc.r111.303990
  • 10.1093/jn/131.5.1405
  • 10.1111/j.1753-4887.2004.tb00053.x
  • 10.1146/annurev.nutr.25.050304.092614
  • 10.1152/physiol.00001.2010
  • 10.3390/nu3010063
 Korenbrot JI. Speed, sensitivity, and stability of the light response in rod and cone photoreceptors: Facts and models. Progress in Retinal and Eye Research. 2012 Sep;31(5):442–66. doi: 10.1016/j.preteyeres.2012.05.002.; von Lintig J. Metabolism of Carotenoids and Retinoids Related to Vision. Journal of Biological Chemistry. 2012 Jan;287(3):1627–34. doi: 10.1074/jbc.r111.303990.; Kefalov VJ. Rod and Cone Visual Pigments and Phototransduction through Pharmacological, Genetic, and Physiological Approaches. Journal of Biological Chemistry. 2012 Jan;287(3):1635–41. doi: 10.1074/jbc.r111.303008.; Wang J, Kefalov VJ. The Cone-specific visual cycle. Progress in Retinal and Eye Research. 2011 Mar;30(2):115–28. doi: 10.1016/j.preteyeres.2010.11.001.; D'Ambrosio DN, Clugston RD, Blaner WS. Vitamin A metabolism: an update. Nutrients. 2011 Jan;3(1):63–103. PMID: 21350678; PMCID: PMC3042718.; von Lintig J, Kiser PD, Golczak M, Palczewski K. The biochemical and structural basis for trans-to-cis isomerization of retinoids in the chemistry of vision. Trends in Biochemical Sciences. 2010 Jul;35(7):400–10. doi: 10.1016/j.tibs.2010.01.005.; Burns ME, Pugh EN. Lessons from photoreceptors: turning off g-protein signaling in living cells. Physiology (Bethesda). 2010 Apr;25(2):72–84. PMID: 20430952; PMCID: PMC2880230.; Blomhoff R, Blomhoff HK. Overview of retinoid metabolism and function. J Neurobiol. 2006 Jun;66(7):606–30. doi: 10.1002/neu.20242. PMID: 16688755.; Harrison EH. Mechanisms of digestion and absorption of dietary vitamin A. Annu Rev Nutr. 2005;25():87–103. doi: 10.1146/annurev.nutr.25.050304.092614. PMID: 16011460.; Wolf G. The visual cycle of the cone photoreceptors of the retina. Nutr Rev. 2004 Jul;62(7 Pt 1):283–6. doi: 10.1111/j.1753-4887.2004.tb00053.x. PMID: 15384919.; Harrison EH, Hussain MM. Mechanisms Involved in the Intestinal Digestion and Absorption of Dietary Vitamin A. The Journal of Nutrition. 2001 May;131(5):1405–8. doi: 10.1093/jn/131.5.1405.; Pugh EN, Lamb TD. Amplification and kinetics of the activation steps in phototransduction. Biochimica et Biophysica Acta (BBA) - Bioenergetics. 1993 Mar;1141(2-3):111–49. doi: 10.1016/0005-2728(93)90038-h.
RA biosynthesis pathway

Accession ID: Reactome:R-DDI-5365859
  • 10.1016/j.bbalip.2011.05.004
  • 10.1016/j.bmc.2013.11.025
 Das BC, Thapa P, Karki R, Das S, Mahapatra S, Liu T, Torregroza I, Wallace DP, Kambhampati S, Van Veldhuizen P, Verma A, Ray SK, Evans T. Retinoic acid signaling pathways in development and diseases. Bioorganic & Medicinal Chemistry. 2014 Jan;22(2):673–83. doi: 10.1016/j.bmc.2013.11.025.; Napoli JL. Physiological insights into all-trans-retinoic acid biosynthesis. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 2012 Jan;1821(1):152–67. doi: 10.1016/j.bbalip.2011.05.004.
Signaling by Nuclear Receptors

Accession ID: Reactome:R-DME-9006931
  • 10.1016/0039-128x(96)00030-x
  • 10.1016/bs.ctdb.2017.02.003
  • 10.1016/j.bbamcr.2009.11.012
  • 10.1016/j.bbamcr.2016.06.004
  • 10.1016/j.mce.2013.06.021
  • 10.1038/nrm.2016.122
  • 10.1210/me.2013-1334
 Holzer G, Markov GV, Laudet V. Evolution of Nuclear Receptors and Ligand Signaling: Toward a Soft Key-Lock Model? Curr Top Dev Biol. 2017;125():1–38. doi: 10.1016/bs.ctdb.2017.02.003. PMID: 28527568.; Levin ER, Hammes SR. Nuclear receptors outside the nucleus: extranuclear signalling by steroid receptors. Nature Reviews Molecular Cell Biology. 2016 Oct 12;17(12):783–97. doi: 10.1038/nrm.2016.122.; Schwartz N, Verma A, Bivens CB, Schwartz Z, Boyan BD. Rapid steroid hormone actions via membrane receptors. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 2016 Sep;1863(9):2289–98. doi: 10.1016/j.bbamcr.2016.06.004.; Simons SS, Edwards DP, Kumar R. Minireview: dynamic structures of nuclear hormone receptors: new promises and challenges. Mol Endocrinol. 2014 Feb;28(2):173–82. PMID: 24284822; PMCID: PMC3896641.; Hah N, Kraus WL. Hormone-regulated transcriptomes: Lessons learned from estrogen signaling pathways in breast cancer cells. Molecular and Cellular Endocrinology. 2014 Jan;382(1):652–64. doi: 10.1016/j.mce.2013.06.021.; Echeverria PC, Picard D. Molecular chaperones, essential partners of steroid hormone receptors for activity and mobility. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 2010 Jun;1803(6):641–9. doi: 10.1016/j.bbamcr.2009.11.012.; Beato M, Chávez S, Truss M. Transcriptional regulation by steroid hormones. Steroids. 1996 Apr;61(4):240–51. doi: 10.1016/0039-128x(96)00030-x. PMID: 8733009.
The retinoid cycle in cones (daylight vision)

Accession ID: Reactome:R-GGA-2187335
  • 10.1016/j.preteyeres.2010.11.001
  • 10.1074/jbc.r111.303008
  • 10.1074/jbc.r111.303990
  • 10.1111/j.1753-4887.2004.tb00053.x
 von Lintig J. Metabolism of Carotenoids and Retinoids Related to Vision. Journal of Biological Chemistry. 2012 Jan;287(3):1627–34. doi: 10.1074/jbc.r111.303990.; Kefalov VJ. Rod and Cone Visual Pigments and Phototransduction through Pharmacological, Genetic, and Physiological Approaches. Journal of Biological Chemistry. 2012 Jan;287(3):1635–41. doi: 10.1074/jbc.r111.303008.; Wang J, Kefalov VJ. The Cone-specific visual cycle. Progress in Retinal and Eye Research. 2011 Mar;30(2):115–28. doi: 10.1016/j.preteyeres.2010.11.001.; Wolf G. The visual cycle of the cone photoreceptors of the retina. Nutr Rev. 2004 Jul;62(7 Pt 1):283–6. doi: 10.1111/j.1753-4887.2004.tb00053.x. PMID: 15384919.
Signaling by Retinoic Acid

Accession ID: Reactome:R-GGA-5362517
  • 10.1016/j.bbalip.2011.05.004
  • 10.1016/j.bbalip.2011.06.002
  • 10.1016/j.bmc.2013.11.025
  • 10.1146/annurev-nutr-072610-145127
 Das BC, Thapa P, Karki R, Das S, Mahapatra S, Liu T, Torregroza I, Wallace DP, Kambhampati S, Van Veldhuizen P, Verma A, Ray SK, Evans T. Retinoic acid signaling pathways in development and diseases. Bioorganic & Medicinal Chemistry. 2014 Jan;22(2):673–83. doi: 10.1016/j.bmc.2013.11.025.; Harrison EH. Mechanisms involved in the intestinal absorption of dietary vitamin A and provitamin A carotenoids. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 2012 Jan;1821(1):70–7. doi: 10.1016/j.bbalip.2011.06.002.; Napoli JL. Physiological insights into all-trans-retinoic acid biosynthesis. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 2012 Jan;1821(1):152–67. doi: 10.1016/j.bbalip.2011.05.004.; Catharine Ross A, Zolfaghari R. Cytochrome P450s in the Regulation of Cellular Retinoic Acid Metabolism. Annu. Rev. Nutr. 2011 Aug 21;31(1):65–87. doi: 10.1146/annurev-nutr-072610-145127.
The retinoid cycle in cones (daylight vision)

Accession ID: Reactome:R-HSA-2187335
  • 10.1016/j.preteyeres.2010.11.001
  • 10.1074/jbc.r111.303008
  • 10.1074/jbc.r111.303990
  • 10.1111/j.1753-4887.2004.tb00053.x
 von Lintig J. Metabolism of Carotenoids and Retinoids Related to Vision. Journal of Biological Chemistry. 2012 Jan;287(3):1627–34. doi: 10.1074/jbc.r111.303990.; Kefalov VJ. Rod and Cone Visual Pigments and Phototransduction through Pharmacological, Genetic, and Physiological Approaches. Journal of Biological Chemistry. 2012 Jan;287(3):1635–41. doi: 10.1074/jbc.r111.303008.; Wang J, Kefalov VJ. The Cone-specific visual cycle. Progress in Retinal and Eye Research. 2011 Mar;30(2):115–28. doi: 10.1016/j.preteyeres.2010.11.001.; Wolf G. The visual cycle of the cone photoreceptors of the retina. Nutr Rev. 2004 Jul;62(7 Pt 1):283–6. doi: 10.1111/j.1753-4887.2004.tb00053.x. PMID: 15384919.
Signaling by Retinoic Acid

Accession ID: Reactome:R-HSA-5362517
  • 10.1016/j.bbalip.2011.05.004
  • 10.1016/j.bbalip.2011.06.002
  • 10.1016/j.bmc.2013.11.025
  • 10.1146/annurev-nutr-072610-145127
 Das BC, Thapa P, Karki R, Das S, Mahapatra S, Liu T, Torregroza I, Wallace DP, Kambhampati S, Van Veldhuizen P, Verma A, Ray SK, Evans T. Retinoic acid signaling pathways in development and diseases. Bioorganic & Medicinal Chemistry. 2014 Jan;22(2):673–83. doi: 10.1016/j.bmc.2013.11.025.; Harrison EH. Mechanisms involved in the intestinal absorption of dietary vitamin A and provitamin A carotenoids. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 2012 Jan;1821(1):70–7. doi: 10.1016/j.bbalip.2011.06.002.; Napoli JL. Physiological insights into all-trans-retinoic acid biosynthesis. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 2012 Jan;1821(1):152–67. doi: 10.1016/j.bbalip.2011.05.004.; Catharine Ross A, Zolfaghari R. Cytochrome P450s in the Regulation of Cellular Retinoic Acid Metabolism. Annu. Rev. Nutr. 2011 Aug 21;31(1):65–87. doi: 10.1146/annurev-nutr-072610-145127.
Disease

Accession ID: Reactome:R-HSA-1643685
  • 10.1002/14651858.cd011076.pub2
  • 10.1002/pro.3936
  • 10.1007/s12272-020-01225-2
  • 10.1007/s40263-014-0155-5
  • 10.1016/0922-4106(93)90072-h
  • 10.1016/j.canlet.2008.04.018
  • 10.1016/j.canlet.2017.10.033
  • 10.1016/j.freeradbiomed.2018.12.033
  • 10.1016/j.msard.2020.102335
  • 10.1021/tx0502138
  • 10.1021/tx100389r
  • 10.1038/ni.1831
  • 10.1038/s41467-020-18764-3
  • 10.1038/s41573-018-0008-x
  • 10.1038/s42003-021-02250-7
  • 10.1073/pnas.0307301101
  • 10.1074/jbc.m000228200
  • 10.1074/jbc.m202196200
  • 10.1083/jcb.200408064
  • 10.1091/mbc.e10-04-0338
  • 10.1101/2021.03.25.437060
  • 10.1111/febs.15485
  • 10.1126/science.279.5350.558
  • 10.1128/mcb.00099-20
  • 10.1128/mcb.23.22.8137-8151.2003
  • 10.1146/annurev.cellbio.22.010305.104219
  • 10.1242/jcs.00500
  • 10.1242/jcs.02528
  • 10.1371/journal.pone.0120254
  • 10.17179/excli2020-2487
  • 10.3727/096504020x15828892654385
 Javorsky A, Humbert PO, Kvansakul M. Structural basis of coronavirus E protein interactions with human PALS1 PDZ domain. Communications Biology. 2021 Jun 11;4(1):724. doi: 10.1038/s42003-021-02250-7.; Ordonez AA, Bullen CK, Villabona-Rueda AF, Thompson EA, Turner ML, Davis SL, Komm O, Powell JD, D'Alessio FR, Yolken RH, Jain SK, Jones-Brando L. Sulforaphane exhibits in vitro and in vivo antiviral activity against pandemic SARS-CoV-2 and seasonal HCoV-OC43 coronaviruses. bioRxiv. 2021 Mar 25;(). PMID: 33791708; PMCID: PMC8010735.; Olagnier D, Farahani E, Thyrsted J, Blay-Cadanet J, Herengt A, Idorn M, Hait A, Hernaez B, Knudsen A, Iversen MB, Schilling M, Jørgensen SE, Thomsen M, Reinert LS, Lappe M, Hoang H, Gilchrist VH, Hansen AL, Ottosen R, Nielsen CG, Møller C, van der Horst D, Peri S, Balachandran S, Huang J, Jakobsen M, Svenningsen EB, Poulsen TB, Bartsch L, Thielke AL, Luo Y, Alain T, Rehwinkel J, Alcamí A, Hiscott J, Mogensen TH, Paludan SR, Holm CK. 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Sulforaphane: Expected to Become a Novel Antitumor Compound. oncol res. 2020 Sep 01;28(4):439–46. doi: 10.3727/096504020x15828892654385.; Unni S, Deshmukh P, Krishnappa G, Kommu P, Padmanabhan B. Structural insights into the multiple binding modes of Dimethyl Fumarate (DMF) and its analogs to the Kelch domain of Keap1. FEBS J. 2021 Mar;288(5):1599–613. doi: 10.1111/febs.15485. PMID: 32672401.; Baird L, Yamamoto M. The Molecular Mechanisms Regulating the KEAP1-NRF2 Pathway. Molecular and Cellular Biology. 2020 Jun 15;40(13). doi: 10.1128/mcb.00099-20.; Kamal MM, Akter S, Lin C, Nazzal S. Sulforaphane as an anticancer molecule: mechanisms of action, synergistic effects, enhancement of drug safety, and delivery systems. Archives of Pharmacal Research. 2020 Mar 10;43(4):371–84. doi: 10.1007/s12272-020-01225-2.; McGuinness G, Kim Y. Sulforaphane treatment for autism spectrum disorder: A systematic review. EXCLI J. 2020;19():892–903. 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PMID: 25900414; PMCID: PMC10663978.; Brennan MS, Matos MF, Li B, Hronowski X, Gao B, Juhasz P, Rhodes KJ, Scannevin RH. Dimethyl Fumarate and Monoethyl Fumarate Exhibit Differential Effects on KEAP1, NRF2 Activation, and Glutathione Depletion In Vitro. PLoS ONE. 2015 Mar 20;10(3):e0120254. doi: 10.1371/journal.pone.0120254.; Burness CB, Deeks ED. Dimethyl fumarate: a review of its use in patients with relapsing-remitting multiple sclerosis. CNS Drugs. 2014 Apr;28(4):373–87. doi: 10.1007/s40263-014-0155-5. PMID: 24623127.; Hu C, Eggler AL, Mesecar AD, van Breemen RB. Modification of keap1 cysteine residues by sulforaphane. Chem Res Toxicol. 2011 Apr 18;24(4):515–21. PMID: 21391649; PMCID: PMC3086360.; Teoh KT, Siu YL, Chan WL, Schlüter MA, Liu CJ, Peiris JS, Bruzzone R, Margolis B, Nal B. The SARS coronavirus E protein interacts with PALS1 and alters tight junction formation and epithelial morphogenesis. Mol Biol Cell. 2010 Nov 15;21(22):3838–52. PMID: 20861307; PMCID: PMC2982091.; Zhou R, Tardivel A, Thorens B, Choi I, Tschopp J. Thioredoxin-interacting protein links oxidative stress to inflammasome activation. Nat Immunol. 2010 Feb;11(2):136–40. doi: 10.1038/ni.1831. PMID: 20023662.; Clarke JD, Dashwood RH, Ho E. Multi-targeted prevention of cancer by sulforaphane. Cancer Letters. 2008 Oct;269(2):291–304. doi: 10.1016/j.canlet.2008.04.018.; Shin K, Fogg VC, Margolis B. Tight junctions and cell polarity. Annu Rev Cell Dev Biol. 2006;22():207–35. doi: 10.1146/annurev.cellbio.22.010305.104219. PMID: 16771626.; Hong F, Freeman ML, Liebler DC. Identification of sensor cysteines in human Keap1 modified by the cancer chemopreventive agent sulforaphane. Chem Res Toxicol. 2005 Dec;18(12):1917–26. doi: 10.1021/tx0502138. PMID: 16359182.; Michel D, Arsanto JP, Massey-Harroche D, Béclin C, Wijnholds J, Le Bivic A. PATJ connects and stabilizes apical and lateral components of tight junctions in human intestinal cells. J Cell Sci. 2005 Sep 01;118(Pt 17):4049–57. doi: 10.1242/jcs.02528. PMID: 16129888.; Shin K, Straight S, Margolis B. PATJ regulates tight junction formation and polarity in mammalian epithelial cells. J Cell Biol. 2005 Feb 27;168(5):705–11. PMID: 15738264; PMCID: PMC2171825.; Wakabayashi N, Dinkova-Kostova AT, Holtzclaw WD, Kang MI, Kobayashi A, Yamamoto M, Kensler TW, Talalay P. Protection against electrophile and oxidant stress by induction of the phase 2 response: fate of cysteines of the Keap1 sensor modified by inducers. Proc Natl Acad Sci U S A. 2004 Feb 17;101(7):2040–5. PMID: 14764894; PMCID: PMC357048.; Zhang DD, Hannink M. Distinct Cysteine Residues in Keap1 Are Required for Keap1-Dependent Ubiquitination of Nrf2 and for Stabilization of Nrf2 by Chemopreventive Agents and Oxidative Stress. Molecular and Cellular Biology. 2003 Nov 01;23(22):8137–51. doi: 10.1128/mcb.23.22.8137-8151.2003.; Roh MH, Fan S, Liu CJ, Margolis B. The Crumbs3-Pals1 complex participates in the establishment of polarity in mammalian epithelial cells. J Cell Sci. 2003 Jul 15;116(Pt 14):2895–906. doi: 10.1242/jcs.00500. PMID: 12771187.; Lemmers C, Médina E, Delgrossi MH, Michel D, Arsanto JP, Le Bivic A. hINADl/PATJ, a homolog of discs lost, interacts with crumbs and localizes to tight junctions in human epithelial cells. J Biol Chem. 2002 Jul 12;277(28):25408–15. doi: 10.1074/jbc.m202196200. PMID: 11964389.; Lind U, Greenidge P, Gillner M, Koehler KF, Wright A, Carlstedt-Duke J. Functional probing of the human glucocorticoid receptor steroid-interacting surface by site-directed mutagenesis. Gln-642 plays an important role in steroid recognition and binding. J Biol Chem. 2000 Jun 23;275(25):19041–9. doi: 10.1074/jbc.m000228200. PMID: 10747884.; Han J, Luby-Phelps K, Das B, Shu X, Xia Y, Mosteller RD, Krishna UM, Falck JR, White MA, Broek D. Role of substrates and products of PI 3-kinase in regulating activation of Rac-related guanosine triphosphatases by Vav. Science. 1998 Jan 23;279(5350):558–60. doi: 10.1126/science.279.5350.558. PMID: 9438848.; Rupprecht R, Reul JMHM, van Steensel B, Spengler D, Söder M, Berning B, Holsboer F, Damm K. Pharmacological and functional characterization of human mineralocorticoid and glucocorticoid receptor ligands. European Journal of Pharmacology: Molecular Pharmacology. 1993 Oct;247(2):145–54. doi: 10.1016/0922-4106(93)90072-h.
Signaling Pathways

Accession ID: Reactome:R-MMU-162582
  • 10.1016/j.bbcan.2006.09.001
  • 10.1016/j.cell.2007.06.009
  • 10.1016/j.cell.2009.03.045
  • 10.1016/j.cytogfr.2004.04.003
  • 10.1016/j.cytogfr.2005.01.001
  • 10.1016/j.devcel.2009.06.016
  • 10.1016/j.tcb.2009.05.008
  • 10.1016/j.tibs.2005.10.005
  • 10.1038/414799a
  • 10.1038/nature08144
  • 10.1038/nrm1498
  • 10.1038/nrm2299
  • 10.1038/nrm2717
  • 10.1038/nrm2803
  • 10.1038/nrm3048
  • 10.1038/sj.onc.1210394
  • 10.1093/jb/mvp148
  • 10.1098/rstb.2006.1894
  • 10.1101/gad.1653708
  • 10.3109/09687688.2011.603101
 Avraham R, Yarden Y. Feedback regulation of EGFR signalling: decision making by early and delayed loops. Nature Reviews Molecular Cell Biology. 2011 Jan 21;12(2):104–17. doi: 10.1038/nrm3048.; Citi S, Spadaro D, Schneider Y, Stutz J, Pulimeno P. Regulation of small GTPases at epithelial cell-cell junctions. Mol Membr Biol. 2011 Oct;28(7-8):427–44. doi: 10.3109/09687688.2011.603101. PMID: 21781017.; Ritter SL, Hall RA. Fine-tuning of GPCR activity by receptor-interacting proteins. Nature Reviews Molecular Cell Biology. 2009 Dec;10(12):819–30. doi: 10.1038/nrm2803.; Miyazono K, Kamiya Y, Morikawa M. Bone morphogenetic protein receptors and signal transduction. Journal of Biochemistry. 2009 Sep 17;147(1):35–51. doi: 10.1093/jb/mvp148.; Kang JS, Liu C, Derynck R. New regulatory mechanisms of TGF-beta receptor function. Trends Cell Biol. 2009 Aug;19(8):385–94. doi: 10.1016/j.tcb.2009.05.008. PMID: 19648010.; MacDonald BT, Tamai K, He X. Wnt/ß-Catenin Signaling: Components, Mechanisms, and Diseases. Developmental Cell. 2009 Jul;17(1):9–26. doi: 10.1016/j.devcel.2009.06.016.; Angers S, Moon RT. Proximal events in Wnt signal transduction. Nature Reviews Molecular Cell Biology. 2009 Jun 17;10(7):468–77. doi: 10.1038/nrm2717.; Rosenbaum DM, Rasmussen SG, Kobilka BK. The structure and function of G-protein-coupled receptors. Nature. 2009 May 21;459(7245):356–63. PMID: 19458711; PMCID: PMC3967846.; Kopan R, Ilagan MX. The canonical Notch signaling pathway: unfolding the activation mechanism. Cell. 2009 Apr 17;137(2):216–33. PMID: 19379690; PMCID: PMC2827930.; Andrae J, Gallini R, Betsholtz C. Role of platelet-derived growth factors in physiology and medicine. Genes Dev. 2008 May 15;22(10):1276–312. PMID: 18483217; PMCID: PMC2732412.; Oldham WM, Hamm HE. Heterotrimeric G protein activation by G-protein-coupled receptors. Nature Reviews Molecular Cell Biology. 2008 Jan;9(1):60–71. doi: 10.1038/nrm2299.; Manning BD, Cantley LC. AKT/PKB signaling: navigating downstream. Cell. 2007 Jun 29;129(7):1261–74. PMID: 17604717; PMCID: PMC2756685.; McKay MM, Morrison DK. Integrating signals from RTKs to ERK/MAPK. Oncogene. 2007 May 14;26(22):3113–21. doi: 10.1038/sj.onc.1210394. PMID: 17496910.; Hehlgans S, Haase M, Cordes N. Signalling via integrins: Implications for cell survival and anticancer strategies. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer. 2007 Jan;1775(1):163–80. doi: 10.1016/j.bbcan.2006.09.001.; Reichardt LF. Neurotrophin-regulated signalling pathways. Philos Trans R Soc Lond B Biol Sci. 2006 Sep 29;361(1473):1545–64. PMID: 16939974; PMCID: PMC1664664.; Patterson RL, van Rossum DB, Nikolaidis N, Gill DL, Snyder SH. Phospholipase C-gamma: diverse roles in receptor-mediated calcium signaling. Trends Biochem Sci. 2005 Dec;30(12):688–97. doi: 10.1016/j.tibs.2005.10.005. PMID: 16260143.; Eswarakumar VP, Lax I, Schlessinger J. Cellular signaling by fibroblast growth factor receptors. Cytokine Growth Factor Rev. 2005 Apr;16(2):139–49. doi: 10.1016/j.cytogfr.2005.01.001. PMID: 15863030.; Wellbrock C, Karasarides M, Marais R. The RAF proteins take centre stage. Nature Reviews Molecular Cell Biology. 2004 Nov;5(11):875–85. doi: 10.1038/nrm1498.; Xie K, Wei D, Shi Q, Huang S. Constitutive and inducible expression and regulation of vascular endothelial growth factor. Cytokine Growth Factor Rev. 2004 Oct;15(5):297–324. doi: 10.1016/j.cytogfr.2004.04.003. PMID: 15450248.; Saltiel AR, Kahn CR. Insulin signalling and the regulation of glucose and lipid metabolism. Nature. 2001 Dec 13;414(6865):799–806. doi: 10.1038/414799a. PMID: 11742412.
The canonical retinoid cycle in rods (twilight vision)

Accession ID: Reactome:R-MMU-2453902
  • 10.1002/neu.20242
  • 10.1016/j.tibs.2010.01.005
  • 10.1074/jbc.r111.303990
  • 10.3390/nu3010063
 von Lintig J. Metabolism of Carotenoids and Retinoids Related to Vision. Journal of Biological Chemistry. 2012 Jan;287(3):1627–34. doi: 10.1074/jbc.r111.303990.; D'Ambrosio DN, Clugston RD, Blaner WS. Vitamin A metabolism: an update. Nutrients. 2011 Jan;3(1):63–103. PMID: 21350678; PMCID: PMC3042718.; von Lintig J, Kiser PD, Golczak M, Palczewski K. The biochemical and structural basis for trans-to-cis isomerization of retinoids in the chemistry of vision. Trends in Biochemical Sciences. 2010 Jul;35(7):400–10. doi: 10.1016/j.tibs.2010.01.005.; Blomhoff R, Blomhoff HK. Overview of retinoid metabolism and function. J Neurobiol. 2006 Jun;66(7):606–30. doi: 10.1002/neu.20242. PMID: 16688755.
Signaling Pathways

Accession ID: Reactome:R-RNO-162582
  • 10.1016/j.bbcan.2006.09.001
  • 10.1016/j.cell.2007.06.009
  • 10.1016/j.cell.2009.03.045
  • 10.1016/j.cytogfr.2004.04.003
  • 10.1016/j.cytogfr.2005.01.001
  • 10.1016/j.devcel.2009.06.016
  • 10.1016/j.tcb.2009.05.008
  • 10.1016/j.tibs.2005.10.005
  • 10.1038/414799a
  • 10.1038/nature08144
  • 10.1038/nrm1498
  • 10.1038/nrm2299
  • 10.1038/nrm2717
  • 10.1038/nrm2803
  • 10.1038/nrm3048
  • 10.1038/sj.onc.1210394
  • 10.1093/jb/mvp148
  • 10.1098/rstb.2006.1894
  • 10.1101/gad.1653708
  • 10.3109/09687688.2011.603101
 Avraham R, Yarden Y. Feedback regulation of EGFR signalling: decision making by early and delayed loops. Nature Reviews Molecular Cell Biology. 2011 Jan 21;12(2):104–17. doi: 10.1038/nrm3048.; Citi S, Spadaro D, Schneider Y, Stutz J, Pulimeno P. Regulation of small GTPases at epithelial cell-cell junctions. Mol Membr Biol. 2011 Oct;28(7-8):427–44. doi: 10.3109/09687688.2011.603101. PMID: 21781017.; Ritter SL, Hall RA. Fine-tuning of GPCR activity by receptor-interacting proteins. Nature Reviews Molecular Cell Biology. 2009 Dec;10(12):819–30. doi: 10.1038/nrm2803.; Miyazono K, Kamiya Y, Morikawa M. Bone morphogenetic protein receptors and signal transduction. Journal of Biochemistry. 2009 Sep 17;147(1):35–51. doi: 10.1093/jb/mvp148.; Kang JS, Liu C, Derynck R. New regulatory mechanisms of TGF-beta receptor function. Trends Cell Biol. 2009 Aug;19(8):385–94. doi: 10.1016/j.tcb.2009.05.008. PMID: 19648010.; MacDonald BT, Tamai K, He X. Wnt/ß-Catenin Signaling: Components, Mechanisms, and Diseases. Developmental Cell. 2009 Jul;17(1):9–26. doi: 10.1016/j.devcel.2009.06.016.; Angers S, Moon RT. Proximal events in Wnt signal transduction. Nature Reviews Molecular Cell Biology. 2009 Jun 17;10(7):468–77. doi: 10.1038/nrm2717.; Rosenbaum DM, Rasmussen SG, Kobilka BK. The structure and function of G-protein-coupled receptors. Nature. 2009 May 21;459(7245):356–63. PMID: 19458711; PMCID: PMC3967846.; Kopan R, Ilagan MX. The canonical Notch signaling pathway: unfolding the activation mechanism. Cell. 2009 Apr 17;137(2):216–33. PMID: 19379690; PMCID: PMC2827930.; Andrae J, Gallini R, Betsholtz C. Role of platelet-derived growth factors in physiology and medicine. Genes Dev. 2008 May 15;22(10):1276–312. PMID: 18483217; PMCID: PMC2732412.; Oldham WM, Hamm HE. Heterotrimeric G protein activation by G-protein-coupled receptors. Nature Reviews Molecular Cell Biology. 2008 Jan;9(1):60–71. doi: 10.1038/nrm2299.; Manning BD, Cantley LC. AKT/PKB signaling: navigating downstream. Cell. 2007 Jun 29;129(7):1261–74. PMID: 17604717; PMCID: PMC2756685.; McKay MM, Morrison DK. Integrating signals from RTKs to ERK/MAPK. Oncogene. 2007 May 14;26(22):3113–21. doi: 10.1038/sj.onc.1210394. PMID: 17496910.; Hehlgans S, Haase M, Cordes N. Signalling via integrins: Implications for cell survival and anticancer strategies. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer. 2007 Jan;1775(1):163–80. doi: 10.1016/j.bbcan.2006.09.001.; Reichardt LF. Neurotrophin-regulated signalling pathways. Philos Trans R Soc Lond B Biol Sci. 2006 Sep 29;361(1473):1545–64. PMID: 16939974; PMCID: PMC1664664.; Patterson RL, van Rossum DB, Nikolaidis N, Gill DL, Snyder SH. Phospholipase C-gamma: diverse roles in receptor-mediated calcium signaling. Trends Biochem Sci. 2005 Dec;30(12):688–97. doi: 10.1016/j.tibs.2005.10.005. PMID: 16260143.; Eswarakumar VP, Lax I, Schlessinger J. Cellular signaling by fibroblast growth factor receptors. Cytokine Growth Factor Rev. 2005 Apr;16(2):139–49. doi: 10.1016/j.cytogfr.2005.01.001. PMID: 15863030.; Wellbrock C, Karasarides M, Marais R. The RAF proteins take centre stage. Nature Reviews Molecular Cell Biology. 2004 Nov;5(11):875–85. doi: 10.1038/nrm1498.; Xie K, Wei D, Shi Q, Huang S. Constitutive and inducible expression and regulation of vascular endothelial growth factor. Cytokine Growth Factor Rev. 2004 Oct;15(5):297–324. doi: 10.1016/j.cytogfr.2004.04.003. PMID: 15450248.; Saltiel AR, Kahn CR. Insulin signalling and the regulation of glucose and lipid metabolism. Nature. 2001 Dec 13;414(6865):799–806. doi: 10.1038/414799a. PMID: 11742412.
Signaling by Nuclear Receptors

Accession ID: Reactome:R-RNO-9006931
  • 10.1016/0039-128x(96)00030-x
  • 10.1016/bs.ctdb.2017.02.003
  • 10.1016/j.bbamcr.2009.11.012
  • 10.1016/j.bbamcr.2016.06.004
  • 10.1016/j.mce.2013.06.021
  • 10.1038/nrm.2016.122
  • 10.1210/me.2013-1334
 Holzer G, Markov GV, Laudet V. Evolution of Nuclear Receptors and Ligand Signaling: Toward a Soft Key-Lock Model? Curr Top Dev Biol. 2017;125():1–38. doi: 10.1016/bs.ctdb.2017.02.003. PMID: 28527568.; Levin ER, Hammes SR. Nuclear receptors outside the nucleus: extranuclear signalling by steroid receptors. Nature Reviews Molecular Cell Biology. 2016 Oct 12;17(12):783–97. doi: 10.1038/nrm.2016.122.; Schwartz N, Verma A, Bivens CB, Schwartz Z, Boyan BD. Rapid steroid hormone actions via membrane receptors. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 2016 Sep;1863(9):2289–98. doi: 10.1016/j.bbamcr.2016.06.004.; Simons SS, Edwards DP, Kumar R. Minireview: dynamic structures of nuclear hormone receptors: new promises and challenges. Mol Endocrinol. 2014 Feb;28(2):173–82. PMID: 24284822; PMCID: PMC3896641.; Hah N, Kraus WL. Hormone-regulated transcriptomes: Lessons learned from estrogen signaling pathways in breast cancer cells. Molecular and Cellular Endocrinology. 2014 Jan;382(1):652–64. doi: 10.1016/j.mce.2013.06.021.; Echeverria PC, Picard D. Molecular chaperones, essential partners of steroid hormone receptors for activity and mobility. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 2010 Jun;1803(6):641–9. doi: 10.1016/j.bbamcr.2009.11.012.; Beato M, Chávez S, Truss M. Transcriptional regulation by steroid hormones. Steroids. 1996 Apr;61(4):240–51. doi: 10.1016/0039-128x(96)00030-x. PMID: 8733009.
The canonical retinoid cycle in rods (twilight vision)

Accession ID: Reactome:R-SSC-2453902
  • 10.1002/neu.20242
  • 10.1016/j.tibs.2010.01.005
  • 10.1074/jbc.r111.303990
  • 10.3390/nu3010063
 von Lintig J. Metabolism of Carotenoids and Retinoids Related to Vision. Journal of Biological Chemistry. 2012 Jan;287(3):1627–34. doi: 10.1074/jbc.r111.303990.; D'Ambrosio DN, Clugston RD, Blaner WS. Vitamin A metabolism: an update. Nutrients. 2011 Jan;3(1):63–103. PMID: 21350678; PMCID: PMC3042718.; von Lintig J, Kiser PD, Golczak M, Palczewski K. The biochemical and structural basis for trans-to-cis isomerization of retinoids in the chemistry of vision. Trends in Biochemical Sciences. 2010 Jul;35(7):400–10. doi: 10.1016/j.tibs.2010.01.005.; Blomhoff R, Blomhoff HK. Overview of retinoid metabolism and function. J Neurobiol. 2006 Jun;66(7):606–30. doi: 10.1002/neu.20242. PMID: 16688755.
RA biosynthesis pathway

Accession ID: Reactome:R-SSC-5365859
  • 10.1016/j.bbalip.2011.05.004
  • 10.1016/j.bmc.2013.11.025
 Das BC, Thapa P, Karki R, Das S, Mahapatra S, Liu T, Torregroza I, Wallace DP, Kambhampati S, Van Veldhuizen P, Verma A, Ray SK, Evans T. Retinoic acid signaling pathways in development and diseases. Bioorganic & Medicinal Chemistry. 2014 Jan;22(2):673–83. doi: 10.1016/j.bmc.2013.11.025.; Napoli JL. Physiological insights into all-trans-retinoic acid biosynthesis. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 2012 Jan;1821(1):152–67. doi: 10.1016/j.bbalip.2011.05.004.
The canonical retinoid cycle in rods (twilight vision)

Accession ID: Reactome:R-XTR-2453902
  • 10.1002/neu.20242
  • 10.1016/j.tibs.2010.01.005
  • 10.1074/jbc.r111.303990
  • 10.3390/nu3010063
 von Lintig J. Metabolism of Carotenoids and Retinoids Related to Vision. Journal of Biological Chemistry. 2012 Jan;287(3):1627–34. doi: 10.1074/jbc.r111.303990.; D'Ambrosio DN, Clugston RD, Blaner WS. Vitamin A metabolism: an update. Nutrients. 2011 Jan;3(1):63–103. PMID: 21350678; PMCID: PMC3042718.; von Lintig J, Kiser PD, Golczak M, Palczewski K. The biochemical and structural basis for trans-to-cis isomerization of retinoids in the chemistry of vision. Trends in Biochemical Sciences. 2010 Jul;35(7):400–10. doi: 10.1016/j.tibs.2010.01.005.; Blomhoff R, Blomhoff HK. Overview of retinoid metabolism and function. J Neurobiol. 2006 Jun;66(7):606–30. doi: 10.1002/neu.20242. PMID: 16688755.
Signaling by Retinoic Acid

Accession ID: Reactome:R-XTR-5362517
  • 10.1016/j.bbalip.2011.05.004
  • 10.1016/j.bbalip.2011.06.002
  • 10.1016/j.bmc.2013.11.025
  • 10.1146/annurev-nutr-072610-145127
 Das BC, Thapa P, Karki R, Das S, Mahapatra S, Liu T, Torregroza I, Wallace DP, Kambhampati S, Van Veldhuizen P, Verma A, Ray SK, Evans T. Retinoic acid signaling pathways in development and diseases. Bioorganic & Medicinal Chemistry. 2014 Jan;22(2):673–83. doi: 10.1016/j.bmc.2013.11.025.; Harrison EH. Mechanisms involved in the intestinal absorption of dietary vitamin A and provitamin A carotenoids. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 2012 Jan;1821(1):70–7. doi: 10.1016/j.bbalip.2011.06.002.; Napoli JL. Physiological insights into all-trans-retinoic acid biosynthesis. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 2012 Jan;1821(1):152–67. doi: 10.1016/j.bbalip.2011.05.004.; Catharine Ross A, Zolfaghari R. Cytochrome P450s in the Regulation of Cellular Retinoic Acid Metabolism. Annu. Rev. Nutr. 2011 Aug 21;31(1):65–87. doi: 10.1146/annurev-nutr-072610-145127.