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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-41943

Kaur, S J; Nerlich, A; Bergmann, S; Rohde, M; Fulde, M; Zähner, D; Hanski, E; Zinkernagel, A S; Nizet, V; Chhatwal, G S; Talay, S R (2010). The CXC chemokine-degrading protease SpyCep of Streptococcus pyogenes promotes its uptake into endothelial cells. The Journal of Biological Chemistry, 285(36):27798-27805.

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Abstract

Streptococcus pyogenes expresses the LPXTG motif-containing cell envelope serine protease SpyCep (also called ScpC, PrtS) that degrades and inactivates the major chemoattractant interleukin 8 (IL-8), thereby impairing host neutrophil recruitment. In this study, we identified a novel function of SpyCep: the ability to mediate uptake into primary human endothelial cells. SpyCep triggered its uptake into endothelial cells but not into human epithelial cells originating from pharynx or lung, indicating an endothelial cell-specific uptake mechanism. SpyCep mediated cellular invasion by an endosomal/lysosomal pathway distinct from the caveolae-mediated invasion pathway of S. pyogenes. Recombinant expression and purification of proteolytically active SpyCep and a series of subfragments allowed functional dissection of the domains responsible for endothelial cell invasion and IL-8 degradation. The N-terminal PR domain was sufficient to mediate endothelial cell invasion, whereas for IL-8-degrading activity, the protease domain and the flanking A domain were required. A polyclonal rabbit serum raised against the recombinant protease efficiently blocked the invasion-mediating activity of SpyCep but not its proteolytic function, further indicating that SpyCep-mediated internalization is independent from its enzymatic activity. SpyCep may thus specifically mediate its own uptake as secreted protein into human endothelial cells.

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8 citations in Web of Science®
8 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Infectious Diseases
DDC:610 Medicine & health
Language:English
Date:2010
Deposited On:11 Jan 2011 16:10
Last Modified:10 Mar 2014 14:47
Publisher:American Society for Biochemistry and Molecular Biology
ISSN:0021-9258
Additional Information:This research was originally published in: Kaur, S J; Nerlich, A; Bergmann, S; Rohde, M; Fulde, M; Zähner, D; Hanski, E; Zinkernagel, A S; Nizet, V; Chhatwal, G S; Talay, S R (2010). The CXC chemokine-degrading protease SpyCep of Streptococcus pyogenes promotes its uptake into endothelial cells. The Journal of Biological Chemistry, 285(36):27798-27805. © the American Society for Biochemistry and Molecular Biology.
Publisher DOI:10.1074/jbc.M109.098053
PubMed ID:20562101

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