Reciprocal regulation of glutathione S-transferase spliceforms and the Drosophila c-Jun N-terminal kinase pathway components

The Biochemical Journal
Rungrutai UdomsinprasertAlbert J Ketterman

Abstract

In mammalian systems, detoxification enzymes of the GST (glutathione S-transferase) family regulate JNK (c-Jun N-terminal kinase) signal transduction by interaction with JNK itself or other proteins upstream in the JNK pathway. In the present study, we have studied GSTs and their interaction with components of the JNK pathway from Diptera. We have evaluated the effects of four Delta class Anopheles dirus GSTs, GSTD1-1, GSTD2-2, GSTD3-3 and GSTD4-4, on the activity of full-length recombinant Drosophila HEP (mitogen-activated protein kinase kinase 7; where HEP stands for hemipterous) and the Drosophila JNK, as well as the reciprocal effect of these kinases on GST activity. Interestingly, even though these four GSTs are alternatively spliced products of the same gene and share >60% identity, they exerted different effects on JNK activity. GSTD1-1 inhibited JNK activity, whereas the other three GST isoforms activated JNK. GSTD2-2, GSTD3-3 and GSTD4-4 were inhibited 50-80% by HEP or JNK but GSTD1-1 was not inhibited by JNK. However, there were some similarities in the actions of HEP and JNK on these GSTs. For example, binding constants for HEP or JNK inhibiting a GST were similar (20-70 nM). Furthermore, after incubation of the GSTs...Continue Reading

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Citations

Nov 23, 2006·Chemical Research in Toxicology·Yakov M KoenRobert P Hanzlik
Dec 15, 2010·The Journal of Biological Chemistry·Huiwen W ZhaoGabriel G Haddad
Nov 22, 2011·Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics·Ramavati PalAlan Clark
Jul 27, 2015·Current Opinion in Immunology·Shirley LuckhartCecilia Giulivi
Oct 9, 2015·Archives of Insect Biochemistry and Physiology·Oleh V LushchakKenneth B Storey
Jun 25, 2020·Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology·Maria M BayliakVolodymyr I Lushchak
Jun 3, 2021·International Journal of Molecular Sciences·Krzysztof LaudanskiKathleen E Sullivan

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