Murine serpin 2A is expressed at high levels in haemopoietic progenitors and down-regulated on differentiation. When it is constitutively expressed in the multipotent haemopoietic cell line, FDCP-Mix, it causes a delay in differentiation and increased clonogenic potential. The serpin is also dramatically up-regulated on T-cell activation. It has an unusual reactive site Cys-Cys sequence, a unique C-terminal extension and lacks a typical cleavable N-terminal signal sequence. In spite of these features, the protein is not a member of the ovalbumin—serpin family, but is instead most closely related to human antichymotrypsin. We have shown that the serpin is intracellular with prominent nuclear localization. Transverse urea gradient gels and CD studies show that the protein undergoes the stressed—relaxed conformational change typical of inhibitory serpins. However, we have not detected complex-forming activity with a set of proteases. Thermal denaturation studies also show that the protein has decreased structural stability under reducing conditions, although it lacks disulphide bonds within the core of the molecule. Our results show that serpin 2A is an intracellular protein with the potential to mediate its biological effects via interaction with non-protease intracellular targets. Furthermore, the results presented suggest a model whereby the serpin interactions could be modulated by redox conditions or conformational change induced by cleavage of the reactive-site loop.
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April 2003
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Research Article|
April 01 2003
Murine serpin 2A is a redox-sensitive intracellular protein Available to Purchase
Emma C. MORRIS;
Emma C. MORRIS
∗Department of Haematology, University College Hospital, Grafton Way, London WC1E 6AU, U.K.
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Timothy R. DAFFORN;
Timothy R. DAFFORN
†Department of Haematology, Wellcome Trust Centre for Molecular Mechanisms in Disease, Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust/MRC Building, Hills Road, Cambridge CB2 2XY, U.K.
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Sharon L. FORSYTH;
Sharon L. FORSYTH
‡Monash University Department of Medicine, Australian Centre for Blood Diseases, Level 5, Clive Ward Centre, Arnold Street, Box Hill 3128, Australia
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Melinda A. MISSEN;
Melinda A. MISSEN
‡Monash University Department of Medicine, Australian Centre for Blood Diseases, Level 5, Clive Ward Centre, Arnold Street, Box Hill 3128, Australia
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Anita J. HORVATH;
Anita J. HORVATH
‡Monash University Department of Medicine, Australian Centre for Blood Diseases, Level 5, Clive Ward Centre, Arnold Street, Box Hill 3128, Australia
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Lynne HAMPSON;
Lynne HAMPSON
§Obstetrics and Gynaecology and Reproductive Health Care, St Mary's Hospital, University of Manchester, Oxford Road, Manchester, U.K.
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Ian N. HAMPSON;
Ian N. HAMPSON
§Obstetrics and Gynaecology and Reproductive Health Care, St Mary's Hospital, University of Manchester, Oxford Road, Manchester, U.K.
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Graeme CURRIE;
Graeme CURRIE
∥School of Botany, University of Melbourne, Parkeville 3010, Australia
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Robin W. CARRELL;
Robin W. CARRELL
†Department of Haematology, Wellcome Trust Centre for Molecular Mechanisms in Disease, Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust/MRC Building, Hills Road, Cambridge CB2 2XY, U.K.
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Paul B. COUGHLIN
Paul B. COUGHLIN
1
‡Monash University Department of Medicine, Australian Centre for Blood Diseases, Level 5, Clive Ward Centre, Arnold Street, Box Hill 3128, Australia
1To whom correspondence should be addressed (e-mail [email protected]).
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Publisher: Portland Press Ltd
Received:
October 08 2002
Accepted:
December 06 2002
Accepted Manuscript online:
December 06 2002
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2003
2003
Biochem J (2003) 371 (1): 165–173.
Article history
Received:
October 08 2002
Accepted:
December 06 2002
Accepted Manuscript online:
December 06 2002
Citation
Emma C. MORRIS, Timothy R. DAFFORN, Sharon L. FORSYTH, Melinda A. MISSEN, Anita J. HORVATH, Lynne HAMPSON, Ian N. HAMPSON, Graeme CURRIE, Robin W. CARRELL, Paul B. COUGHLIN; Murine serpin 2A is a redox-sensitive intracellular protein. Biochem J 1 April 2003; 371 (1): 165–173. doi: https://doi.org/10.1042/bj20021567
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