Superoxide dismutase protects calcineurin from inactivation - PubMed (original) (raw)
. 1996 Oct 3;383(6599):434-7.
doi: 10.1038/383434a0.
Affiliations
- PMID: 8837775
- DOI: 10.1038/383434a0
Superoxide dismutase protects calcineurin from inactivation
X Wang et al. Nature. 1996.
Abstract
Calcineurin is the only protein phosphatase known to be under the control of Ca2+ and calmodulin. It is targeted by immunosuppressive drugs and has a critical role in T-cell activation. It is specifically inhibited by immunosuppressant immunophilin complexes, which enabled its function in regulating a wide range of cellular responses to Ca2+-mobilizing signals to be identified. Calcineurin in situ is 10-20 times more active than in the purified form and is subject to a time- and Ca2+/calmodulin-dependent reversible inactivation that is facilitated by small, heat-stable molecules. Here we identify a factor that prevents the inactivation of calcineurin in vitro and in vivo as the enzyme superoxide dismutase, which indicates that inactivation may be the result of oxidative damage to the Fe-Zn active centre of calcineurin. The redox state of iron provides a mechanism to regulate calcineurin activity by desensitizing the enzyme and coupling Ca2+-dependent protein dephosphorylation to the redox state of the cell. The protection of calcineurin against inactivation by superoxide dismutase constitutes a new physiological role for this enzyme which enables the Ca2+-dependent regulation of cellular processes to be modulated by the redox potential.
Similar articles
- Calcineurin: not just a simple protein phosphatase.
Guerini D. Guerini D. Biochem Biophys Res Commun. 1997 Jun 18;235(2):271-5. doi: 10.1006/bbrc.1997.6802. Biochem Biophys Res Commun. 1997. PMID: 9199180 Review. - Control of a novel adenylyl cyclase by calcineurin.
Paterson JM, Smith SM, Harmar AJ, Antoni FA. Paterson JM, et al. Biochem Biophys Res Commun. 1995 Sep 25;214(3):1000-8. doi: 10.1006/bbrc.1995.2385. Biochem Biophys Res Commun. 1995. PMID: 7575502 - Binding of active cyclosporins to cyclophilin A and B, complex formation with calcineurin A.
Ryffel B, Woerly G, Murray M, Eugster HP, Car B. Ryffel B, et al. Biochem Biophys Res Commun. 1993 Aug 16;194(3):1074-83. doi: 10.1006/bbrc.1993.1931. Biochem Biophys Res Commun. 1993. PMID: 8394698 - Mechanism of Ca(2+)-dependent inactivation of L-type Ca2+ channels in GH3 cells: direct evidence against dephosphorylation by calcineurin.
Victor RG, Rusnak F, Sikkink R, Marban E, O'Rourke B. Victor RG, et al. J Membr Biol. 1997 Mar 1;156(1):53-61. doi: 10.1007/s002329900187. J Membr Biol. 1997. PMID: 9070464 - On the role of calcium during chemotactic signalling and differentiation of the cellular slime mould Dictyostelium discoideum.
Malchow D, Mutzel R, Schlatterer C. Malchow D, et al. Int J Dev Biol. 1996 Feb;40(1):135-9. Int J Dev Biol. 1996. PMID: 8735922 Review.
Cited by
- Direct interaction and reciprocal regulation between ASK1 and calcineurin-NFAT control cardiomyocyte death and growth.
Liu Q, Wilkins BJ, Lee YJ, Ichijo H, Molkentin JD. Liu Q, et al. Mol Cell Biol. 2006 May;26(10):3785-97. doi: 10.1128/MCB.26.10.3785-3797.2006. Mol Cell Biol. 2006. PMID: 16648474 Free PMC article. - Protein phosphatases of Saccharomyces cerevisiae.
Offley SR, Schmidt MC. Offley SR, et al. Curr Genet. 2019 Feb;65(1):41-55. doi: 10.1007/s00294-018-0884-y. Epub 2018 Sep 17. Curr Genet. 2019. PMID: 30225534 Free PMC article. Review. - CaMKII in the cardiovascular system: sensing redox states.
Erickson JR, He BJ, Grumbach IM, Anderson ME. Erickson JR, et al. Physiol Rev. 2011 Jul;91(3):889-915. doi: 10.1152/physrev.00018.2010. Physiol Rev. 2011. PMID: 21742790 Free PMC article. Review. - Hydrogen peroxide modulation of synaptic plasticity.
Kamsler A, Segal M. Kamsler A, et al. J Neurosci. 2003 Jan 1;23(1):269-76. doi: 10.1523/JNEUROSCI.23-01-00269.2003. J Neurosci. 2003. PMID: 12514224 Free PMC article. - Effects of stably incorporated iron on protein phosphatase-1 structure and activity.
Salvi F, Trebacz M, Kokot T, Hoermann B, Rios P, Barabas O, Köhn M. Salvi F, et al. FEBS Lett. 2018 Dec;592(24):4028-4038. doi: 10.1002/1873-3468.13284. Epub 2018 Nov 23. FEBS Lett. 2018. PMID: 30403291 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Miscellaneous