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Prepublished online as a Blood First Edition Paper on July 3, 2003; DOI 10.1182/blood-2003-02-0661. This Article Full Text (PDF) All Versions of this Article: 2003-02-0661v1 102/8/2835    most recent Alert me when this article is cited Alert me if a correction is posted 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 Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Isordia-Salas, I. Articles by Colman, R. W Search for Related Content PubMed PubMed Citation Articles by Isordia-Salas, I. Articles by Colman, R. W Social Bookmarking                   What's this? Submitted March 3, 2003 Accepted June 24, 2003 The mutation S511N leads to N-glycosylation and increases the cleavage of high molecular weight kininogen in rats genetically susceptible to inflammation Irma Isordia-Salas, Robin A Pixley, Hemant Parekh, Satya P Kunapuli, Fengling Li, Anthony Stadnicki, Yingzhang Lin, R Balfour Sartor, and Robert W Colman* The Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, PA, USA Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, PA, USA Center for Gastrointestinal Biology and Disease, University of North Carolina School of Medicine, Chapel Hill, NC, USA * Corresponding author; email: robert.colman{at}temple.edu. Crohn's disease is immunologically mediated and characterized by intestinal and systemic chronic inflammation. In a rat model, injection of peptidoglycan-polysaccharide complexes into the intestinal wall induced chronic inflammation in Lewis but neither Fischer nor Buffalo rats, indicating a differential genetic susceptibility. Proteolysis of plasma high molecular weight kininogen (HK) yielding bradykinin and cleaved HK (HKa), was faster in Lewis than in Fischer or Buffalo rat plasma. A single point mutation at nucleotide 1586 was found translating respectively to Ser511 (Buffalo and Fisher) and Asn511(Lewis). The latter defines a NXT consensus sequence for N-glycosylation. We expressed these domains in E.coli and found no differences in the rate of cleavage by purified kallikrein in the three strains in the absence of N-glycosylation. We then expressed these domains in CHO cells, which are capable of glycosylation and found an increased rate of cleavage of Lewis HK. The Lewis mutation is associated with N-glycosylation as evidenced by a more rapid migration after treatment with N-glycosidase F. When CHO cells were cultured in the presence of tunicamycin the kallikrein- induced cleavage rate of Lewis HK was not increased. This molecular alteration might be one contributing factor resulting in chronic inflammation in Lewis rats. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: P. Roll, G. Rudolf, S. Pereira, B. Royer, I. E. Scheffer, A. Massacrier, M.-P. Valenti, N. Roeckel-Trevisiol, S. Jamali, C. Beclin, et al. SRPX2 mutations in disorders of language cortex and cognition Hum. Mol. Genet., April 1, 2006; 15(7): 1195 - 1207. [Abstract] [Full Text] [PDF] R. G. Espinola, A. Uknis, I. M. Sainz, I. Isordia-Salas, R. Pixley, R. DeLa Cadena, W. Long, A. Agelan, J. Gaughan, A. Adam, et al. A Monoclonal Antibody to High-Molecular Weight Kininogen Is Therapeutic in a Rodent Model of Reactive Arthritis Am. J. Pathol., September 1, 2004; 165(3): 969 - 976. [Abstract] [Full Text] [PDF]

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