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

J. Biol. Chem., Vol. 281, Issue 4, 2380-2389, January 27, 2006

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 281/4/2380    most recent M505986200v1 Alert me when this article is cited 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Weichart, D. Articles by Rosenstiel, P. Search for Related Content PubMed PubMed Citation Articles by Weichart, D. Articles by Rosenstiel, P. Social Bookmarking                      What's this?

Analysis of NOD2-mediated Proteome Response to Muramyl Dipeptide in HEK293 Cells^*

Dieter Weichart, Johan Gobom, Sina Klopfleisch, Robert Häsler, Niklas Gustavsson, Susanne Billmann, Hans Lehrach, Dirk Seegert¶, Stefan Schreiber1, and Philip Rosenstiel

From the Max Planck Institute of Molecular Genetics, D-14195 Berlin-Dahlem, Institute of Clinical Molecular Biology, University Hospital Schleswig-Holstein, D-24105 Kiel, and ^¶Conaris Research Institute AG, D-24105 Kiel, Germany

NOD2, a cytosolic receptor for the bacterial proteoglycan fragment muramyl dipeptide (MDP), plays an important role in the recognition of intracellular pathogens. Variants in the bacterial sensor domain of NOD2 are genetically associated with an increased risk for the development of Crohn disease, a human chronic inflammatory bowel disease. In the present study, global protein expression changes after MDP stimulation were analyzed by two-dimensional PAGE of total protein extracts of human cultured cells stably transfected with expression constructs encoding for wild type NOD2 (NOD2^WT) or the disease-associated NOD2 L1007fsinsC (NOD2^SNP13) variant. Differentially regulated proteins were identified by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) peptide mass fingerprinting and MALDI MS/MS. The limited overlap in the responses of the NOD2-overexpressing cell lines to MDP included a down-regulation of heat shock 70-kDa protein 4. A complex pro-inflammatory program regulated by NOD2^WT that encompasses a regulation of key genes involved in protein folding, DNA repair, cellular redox homeostasis, and metabolism was observed both under normal growth conditions and after stimulation with MDP. By using the comparison of NOD2^WT and disease-associated NOD2^SNP13 variant, we have identified a proteomic signature pattern that may further our understanding of the influence of genetic variations in the NOD2 gene in the pathophysiology of chronic inflammatory bowel disease.

Received for publication, June 1, 2005 , and in revised form, October 18, 2005.

^* This work was supported by Deutsche Forschungsgemeinschaft Grant SFB 415, by the Proteomverbund Competence Network within the National Genome Research Network, the German Ministry for Education and Research, and the European Commission (EU FP5 Genomics of IBD). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains Figs. S1–S4 and Table 1.

¹ To whom correspondence should be addressed: Institute of Clinical Molecular Biology of the University Hospital Schleswig-Holstein, Campus Kiel, Schittenhelmstr. 12, D-24105 Kiel, Germany. Tel.: 49-431-597-1373; Fax: 49-431-597-1842; E-mail: s.schreiber{at}mucosa.de.

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

This article has been cited by other articles:

				A. Till, P. Rosenstiel, K. Brautigam, C. Sina, G. Jacobs, H.-H. Oberg, D. Seegert, T. Chakraborty, and S. Schreiber A role for membrane-bound CD147 in NOD2-mediated recognition of bacterial cytoinvasion J. Cell Sci., February 15, 2008; 121(4): 487 - 495. [Abstract] [Full Text] [PDF]

				S. Fillon, K. Soulis, S. Rajasekaran, H. Benedict-Hamilton, J. N. Radin, C. J. Orihuela, K. C. El Kasmi, G. Murti, D. Kaushal, M. W. Gaber, et al. Platelet-Activating Factor Receptor and Innate Immunity: Uptake of Gram-Positive Bacterial Cell Wall into Host Cells and Cell-Specific Pathophysiology J. Immunol., November 1, 2006; 177(9): 6182 - 6191. [Abstract] [Full Text] [PDF]