HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: M200050-MCP200v1 M200050-MCP200v2 2/7/453    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Glossary Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kim, J. K. Articles by Moscarello, M. A. Search for Related Content PubMed PubMed Citation Articles by Kim, J. K. Articles by Moscarello, M. A. Social Bookmarking                      What's this?

Molecular & Cellular Proteomics 2:453-462, 2003.
© 2003 by The American Society for Biochemistry and Molecular Biology, Inc.

---

Research

Multiple Sclerosis

An Important Role for Post-Translational Modifications of Myelin Basic Protein in Pathogenesis^*

J. K. Kim, F. G. Mastronardi, D. D. Wood, D. M. Lubman, R. Zand^|| and M. A. Moscarello^,¶

From the Department of Chemistry, University of Michigan, Ann Arbor, MI 48109-1055, Structural Biology & Biochemistry, Research Institute, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada, and ^|| Biophysics Research Division and Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109-1055

Myelin basic protein (MBP) represents a candidate autoantigen in multiple sclerosis (MS). We isolated MBP from normal and MS human white matter and purified six components (charge isomers) to compare the post-translational modifications on each. The sites and extent of methylation, deimination, and phosphorylation were documented for all tryptic peptides by mass spectrometry. We found that mono and dimethylated arginine 107 was increased in MS samples; deimination of arginine occurred at a number of sites and was elevated in MS; phosphorylation was observed in 10 peptides in normal samples but was greatly reduced or absent in most peptides from MS samples. Data obtained with MBP isolated from fresh brain obtained from a spontaneously demyelinating mouse model supported the view that the changes observed in human brain were probably related to pathogenesis of demyelination, i.e. we found decreased phosphorylation and decreased amounts of glycogen synthesis kinase in brain homogenates using specific antibodies. This study represents the first to define post-translational modifications in demyelinating disease and suggest an important role in pathogenesis.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				P. Proost, T. Loos, A. Mortier, E. Schutyser, M. Gouwy, S. Noppen, C. Dillen, I. Ronsse, R. Conings, S. Struyf, et al. Citrullination of CXCL8 by peptidylarginine deiminase alters receptor usage, prevents proteolysis, and dampens tissue inflammation J. Exp. Med., September 1, 2008; 205(9): 2085 - 2097. [Abstract] [Full Text] [PDF]

				D. S. Libich and G. Harauz Backbone Dynamics of the 18.5 kDa Isoform of Myelin Basic Protein Reveals Transient {alpha}-Helices and a Calmodulin-Binding Site Biophys. J., June 15, 2008; 94(12): 4847 - 4866. [Abstract] [Full Text] [PDF]

				B. R. Lawson, Y. Manenkova, J. Ahamed, X. Chen, J.-P. Zou, R. Baccala, A. N. Theofilopoulos, and C. Yuan Inhibition of Transmethylation Down-Regulates CD4 T Cell Activation and Curtails Development of Autoimmunity in a Model System J. Immunol., April 15, 2007; 178(8): 5366 - 5374. [Abstract] [Full Text] [PDF]

				F. G. Mastronardi, D. D. Wood, J. Mei, R. Raijmakers, V. Tseveleki, H.-M. Dosch, L. Probert, P. Casaccia-Bonnefil, and M. A. Moscarello Increased Citrullination of Histone H3 in Multiple Sclerosis Brain and Animal Models of Demyelination: A Role for Tumor Necrosis Factor-Induced Peptidylarginine Deiminase 4 Translocation. J. Neurosci., November 1, 2006; 26(44): 11387 - 11396. [Abstract] [Full Text] [PDF]

				A. A. Musse, J. M. Boggs, and G. Harauz From the Cover: Deimination of membrane-bound myelin basic protein in multiple sclerosis exposes an immunodominant epitope PNAS, March 21, 2006; 103(12): 4422 - 4427. [Abstract] [Full Text] [PDF]

				B. Canas, D. Lopez-Ferrer, A. Ramos-Fernandez, E. Camafeita, and E. Calvo Mass spectrometry technologies for proteomics Brief Funct Genomic Proteomic, February 1, 2006; 4(4): 295 - 320. [Abstract] [Full Text] [PDF]

				F. Lolli, B. Mulinacci, A. Carotenuto, B. Bonetti, G. Sabatino, B. Mazzanti, A. M. D'Ursi, E. Novellino, M. Pazzagli, L. Lovato, et al. An N-glucosylated peptide detecting disease-specific autoantibodies, biomarkers of multiple sclerosis PNAS, July 19, 2005; 102(29): 10273 - 10278. [Abstract] [Full Text] [PDF]

				B N Hammack, K Y. Fung, S W Hunsucker, M W Duncan, M P Burgoon, G P Owens, and D H Gilden Proteomic analysis of multiple sclerosis cerebrospinal fluid Multiple Sclerosis, June 1, 2004; 10(3): 245 - 260. [Abstract] [PDF]

				C. C. Wu, M. J. MacCoss, G. Mardones, C. Finnigan, S. Mogelsvang, J. R. Yates III, and K. E. Howell Organellar Proteomics Reveals Golgi Arginine Dimethylation Mol. Biol. Cell, June 1, 2004; 15(6): 2907 - 2919. [Abstract] [Full Text] [PDF]