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 with JNK, both JNK and the GSTs changed catalytic properties. The substrate specificities of both GSTs and JNK were also altered after their co-incubation. In addition, glutathione modulated the effects of JNK on GST activity. These results emphasize that different GST spliceforms possess different properties, both in their catalytic function and in their regulation of signalling through the JNK pathway.
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Research Article|
October 26 2004
Reciprocal regulation of glutathione S-transferase spliceforms and the Drosophila c-Jun N-terminal kinase pathway components
Rungrutai UDOMSINPRASERT;
Rungrutai UDOMSINPRASERT
*Institute of Molecular Biology and Genetics, Mahidol University, Salaya Campus, Nakorn Pathom 73170, Thailand
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Marie A. BOGOYEVITCH;
Marie A. BOGOYEVITCH
†Cell Signalling Laboratory, Biochemistry and Molecular Biology, University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia
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Albert J. KETTERMAN
Albert J. KETTERMAN
1
*Institute of Molecular Biology and Genetics, Mahidol University, Salaya Campus, Nakorn Pathom 73170, Thailand
1To whom correspondence should be addressed (email frakt@mahidol.ac.th).
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Publisher: Portland Press Ltd
Received:
March 30 2004
Revision Received:
June 28 2004
Accepted:
July 13 2004
Accepted Manuscript online:
July 14 2004
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2004
Biochem J (2004) 383 (3): 483–490.
Article history
Received:
March 30 2004
Revision Received:
June 28 2004
Accepted:
July 13 2004
Accepted Manuscript online:
July 14 2004
Citation
Rungrutai UDOMSINPRASERT, Marie A. BOGOYEVITCH, Albert J. KETTERMAN; Reciprocal regulation of glutathione S-transferase spliceforms and the Drosophila c-Jun N-terminal kinase pathway components. Biochem J 1 November 2004; 383 (3): 483–490. doi: https://doi.org/10.1042/BJ20040519
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