Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi


  • Thyaga Raju KedamEmail author
  • Pallavi Chittoor
  • Divya Kurumala
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_28


 GST;  Gsto 1

Historical Background

The Glutathione-S-transferases exist as cytosolic, mitochondrial, and microsomal which can participate in signal transduction by not phosphorylating any factor that is directly involved in which cell growth and death. This signal transduction is considered to be a new way of implication in cell metabolic pathways due to the influence of external, such as xenobiotics and UV radiation, and internal, such as oxidative stress, free radicals, etc., agents. The GST binding assay studies revealed that they participate in the inhibition of various proteins, for example, phosphoproteins, AP-1, JNK, etc., in the systems to regulate cell mechanisms during cell synthesis.

Biomembranes and Signal Transduction

A biomembrane is an enclosing or separating membrane that acts as a selective barrier, within or around a cell. It consists of a lipid bilayer with embedded proteins that may constitute close to 50% of membrane content (Mark Latash 2007). It has a...

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Our department is funded by DST FIST and UGC BSR, New Delhi Grants.


  1. Adler V, Yin Z, Fuchs SY, Benezra M, Rosario L, Tew KD, et al. Regulation of JNK signaling by GSTp. EMBO J. 1999;18:1321–34.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Beato M, Chavez S, Truss M. Transcriptional regulation by steroid hormones. Steroids. 1996;61(4):240–51.PubMedCrossRefGoogle Scholar
  3. Beuckmann CT, Fujimori K, Urade Y, Hayaishi O. Identification of mu-class glutathione transferases M2-2 and M3-3 as cytosolic prostaglandin E synthases in the human brain. Neurochem Res. 2000;25:733–8.PubMedCrossRefGoogle Scholar
  4. Board PG, Coggan M, Chelvanayagam G, Easteal S, Jermiin LS, Schulte GK, et al. Identification, characterization and crystal structure of the omega class glutathione transferases. J Biol Chem. 2000;275:24798–806.PubMedCrossRefGoogle Scholar
  5. Ciaccio PJ, Tew KD, La Creta FP. Enzymatic conjugation of chlorambucil with glutathione by human glutathione S-transferases and inhibition by ethacrynic acid. Biochem Pharmacol. 1991;42:1504–7.PubMedCrossRefGoogle Scholar
  6. Coles B, Nowell SA, MacLeod SL, Sweeney C, Lang NP, Kadlubar FF. The role of human glutathione S-transferases (hGSTs) in the detoxification of the food-derived carcinogen metabolite N-acetoxy-PhIP, and the effect of a polymorphism in hGSTA1 on colorectal cancer risk. Mutat Res. 2001;482:3–10.PubMedCrossRefGoogle Scholar
  7. Cumming RC, Lightfoot J, Beard K, Youssoufian H, O’Brien PJ, Buchwald M. Fanconi anemia group C protein prevents apoptosis in hematopoietic cells through redox regulation of GSTP1. Nat Med. 2001;7(7):814–20.PubMedCrossRefGoogle Scholar
  8. Dang DT, Chen F, Kohli M, Rago C, Cummins JM, Dang LH. Glutathione S-transferase pi1 promotes tumorigenicity in HCT116 human colon cancer cells. Cancer Res. 2005;65:9485–94.PubMedCrossRefGoogle Scholar
  9. Danielson UH, Mannervik B. Kinetic independence of the subunits of cytosolic glutathione transferase from the rat. Biochem J. 1985;231(2):263–7.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Davis RJ. Signal transduction by the JNK group of MAP kinases. Cell. 2000;103:239–52.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Divya K, Kamala K, Swamy MV, Thyagaraju K. Glutathione admits enhanced rate of chick embryo lifespan from lipid degenerative stress during incubation. World J Pharm Res. 2014;3(10):1517.Google Scholar
  12. Dorion S, Lambert H, Landry J. Activation of the p38 signaling pathway by heat shock involves the dissociation of glutathione-S-transferase Mu from Ask1*. J Biol Chem. 2002;277:30792–7.PubMedCrossRefGoogle Scholar
  13. Hammes SR. The further redefining of steroid-mediated signaling. Proc Natl Acad Sci USA. 2003;100(5):2168–70.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Han J, Lee J-D, Bibbs L, Ulevitch RJ. A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells. Science. 1994;265:808–11.PubMedCrossRefGoogle Scholar
  15. Hanna MH, Nowicki JJ, Fatone MA. Extracellular cyclic AMP (cAMP) during development of the cellular slime mold Polysphondylium violaceum: comparison of accumulation in the wild type and an aggregation-defective mutant. J Bacteriol. 1984;157(2):345–9.PubMedPubMedCentralGoogle Scholar
  16. Hayes JD, Flanagan JU, Jowsey IR. Glutathione transferases. Annu Rev Pharmacol Toxicol. 2005;45:51–88.PubMedCrossRefGoogle Scholar
  17. Hunter T. Protein kinases and phosphatases: the yin and yang of protein phosphorylation and signaling. Cell. 1995;80:225–36.PubMedCrossRefGoogle Scholar
  18. Ip YT, Davis RJ. Signal transduction by the c-Jun N-terminal kinase (JNK) – from inflammation to development. Curr Opin Cell Biol. 1998;10:205–19.PubMedCrossRefGoogle Scholar
  19. Ishibashi T, Bottaro DP, Chan A, Miki T, Aaronson SA. Expression cloning of a human dual-specificity phosphatase. Proc Natl Acad Sci USA. 1992;89:12170–4.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Kato Y, Kravchenko VV, Tapping RI, Han J, Ulevitch RJ, Lee JD. BMK1/ERK5 regulates serum-induced early gene expression through transcription factor MEF2C. EMBO J. 1997;16:7054–66.PubMedPubMedCentralCrossRefGoogle Scholar
  21. Kistler J, Stroud RM, et al. Structure and function of an acetylcholine receptor. Biophys J. 1982;37(1):371–83.PubMedPubMedCentralCrossRefGoogle Scholar
  22. Latash ML. Neurophysiological basis of movement. Human Kinetics: Champaign; 2007. isbn:978-0736063676.Google Scholar
  23. Lawler S, Fleming Y, Goedert M, Cohen P. Synergistic activation of SAPK1/JNK1 by two MAP kinase kinases in vitro. Curr Biol. 1998;8:1387–90.PubMedCrossRefGoogle Scholar
  24. Lechner C, Zahalka MA, Giot JF, Møller NP, Ullrich A. ERK6, a mitogen-activated protein kinase involved in C2C12 myoblast differentiation. Proc Natl Acad Sci U S A. 1996;93(9):4355–9.PubMedPubMedCentralCrossRefGoogle Scholar
  25. Lin X, Tascilar M, Lee WH, Vles WJ, Lee BH, Veeraswamy R, Asgari K, Freije D, van Rees B, Gage WR, Bova GS, Isaacs WB, Brooks JD, DeWeese TL, De Marzo AM, Nelson WG. GSTP1 CpG island hypermethylation is responsible for the absence of GSTP1 expression in human prostate cancer cells. Am J Pathol. 2001;159:1815–26.PubMedPubMedCentralCrossRefGoogle Scholar
  26. Mannervik B, Alin P, Guthenberg C, Jensson H, Tahir MK, Warholm M, et al. Identification of three classes of cytosolic glutathione transferase common to several mammalian species: correlation between structural data and enzymatic properties. Proc Natl Acad Sci USA. 1985;82:7202–6.PubMedPubMedCentralCrossRefGoogle Scholar
  27. McLellan RA, Oscarson M, Alexandrie AK, Seidegard J, Evans DA, Rannug A, et al. Characterization of a human glutathione S-transferase mu cluster containing a duplicated GSTM1 gene that causes ultrarapid enzyme activity. Mol Pharmacol. 1997;52:958–65.PubMedCrossRefGoogle Scholar
  28. Musti AM, Treier M, Bohmann D. Reduced ubiquitin-dependent degradation of c-Jun after phosphorylation by MAP kinases. Science. 1997;275:400–2.PubMedCrossRefGoogle Scholar
  29. New L, Han J. The p38 MAP kinase pathway and its biological function. Trends Cardiovasc Med. 1998;8:220–8.PubMedCrossRefGoogle Scholar
  30. Ramgamaltha S, Tew KD. Immunohistochemical localization of glutathione-S-transferases alpha, mu and pi in normal tissue and carcinomas from human colon. Carcinogenesis. 1991;12:2383–7.CrossRefGoogle Scholar
  31. Reece J, Campbell N. Biology. San Francisco: Benjamin Cummings; 2002. isbn:978-0-8053-6624-5.Google Scholar
  32. Rodbell M. The role of hormone receptors and GTP-regulatory proteins in membrane transduction. Nature. 1980;284(5751):17–22.PubMedCrossRefGoogle Scholar
  33. Ruxana Begum SK, Kedam TR. Effect of acrylamide on chick embryo liver GSTs. Med J Nutr Met. 2010;3(1):31–3. Adv Cancer Res. 52:205–55.Google Scholar
  34. Schroder K, et al. Interferon-γ an overview of signals, mechanisms and functions. J Leukoc Biol. 2004;75:163–89.PubMedCrossRefGoogle Scholar
  35. Silverthorn DU. Human physiology. 4th ed. San Francisco: Benjamin Cumming; 2006.Google Scholar
  36. Sprague Jr GF. Signal transduction in yeast mating: receptors, transcription factors, and the kinase connection. Trends Genet. 1991;7(11–12):393–8.PubMedCrossRefGoogle Scholar
  37. Strange RC, Fryer AA. The glutathione S-transferases: influence of polymorphism on cancer susceptibility. IARC Sci Publ. 1999;231–49.Google Scholar
  38. Sugden D, Davidson K, et al. Melatonin, melatonin receptors and melanophores: a moving story. Pigment Cell Res. 2004;17(5):454–60.PubMedCrossRefGoogle Scholar
  39. Tew KD. Glutathione-associated enzymes in anticancer drug resistance. Cancer Res. 1994;54:4313–20.PubMedGoogle Scholar
  40. Tournier C, Dong C, Turner TK, Jones SN, Flavell RA, Davis RJ. MKK7 is an essential component of the JNK signal transduction pathway activated by pro-inflammatory cytokines. Genes Dev. 2001;15:1419–26.PubMedPubMedCentralCrossRefGoogle Scholar
  41. Townsend D, Tew K. Am J Pharmacogenomics. 2003;3:157–72.PubMedCrossRefGoogle Scholar
  42. Wang L, Xu J, Ji C, Gu S, Lv Y, Li S, Xu Y, Xie Y, Mao Y. Cloning, expression and characterization of human glutathione S-transferase Omega 2. Int J Mol Med. 2005;16:19–27.PubMedGoogle Scholar

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© Springer International Publishing AG 2018

Authors and Affiliations

  • Thyaga Raju Kedam
    • 1
    Email author
  • Pallavi Chittoor
    • 1
  • Divya Kurumala
    • 1
  1. 1.Department of BiochemistrySri Venkateswara University College of SciencesTirupatiIndia