This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Beer, S.
Right arrow Articles by Holzmann, B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Beer, S.
Right arrow Articles by Holzmann, B.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, November 2005, p. 9646-9660, Vol. 25, No. 21
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.21.9646-9660.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Impaired Immune Responses and Prolonged Allograft Survival in Sly1 Mutant Mice

Sandra Beer,1,2,{dagger} Tanja Scheikl,1,{dagger} Bernhard Reis,2,{dagger} Norbert Hüser,1 Klaus Pfeffer,2 and Bernhard Holzmann1*

Department of Surgery, Technische Universität München, 81675 Munich, Germany,1 Institute of Medical Microbiology, Universität Düsseldorf, 40225 Düsseldorf, Germany2

Received 4 July 2005/ Accepted 27 July 2005

Adaptive immunity is crucial for protective host defense and the development of immunological disorders. SLY1 was recently identified as an X-chromosomal SH3 protein that is serine phosphorylated (Ser27) upon B-and T-cell receptor engagement. Here, we demonstrate that SLY1 is localized in the cytoplasm and the nucleus of immunocytes. We generated mice expressing a mutant version of SLY1 lacking Ser27 and a functional nuclear localization signal. The defective SLY1 (SLY1d) protein is localized exclusively in the cytoplasm. B- and T-cell proliferation is attenuated and T-cell cytokine production is severely reduced. Sly1d/d mice exhibit reduced lymphoid organ sizes, diminished marginal zone B-cell numbers, and severely impaired antibody responses against T-dependent and -independent antigens. Importantly, survival of semi-identical cardiac allografts was substantially prolonged in Sly1d/d mice. These results define SLY1 as an essential molecular component for the full activation of adaptive immunity.

* Corresponding author. Mailing address: Department of Surgery, Technische Universität München, Ismaninger Strasse 22, 81675 Munich, Germany. Phone: 49-89-4140 2033. Fax: 49-89-4140 6605. E-mail: holzmann{at}nt1.chir.med.tu-muenchen.de.

{dagger} These authors contributed equally to this work.

Molecular and Cellular Biology, November 2005, p. 9646-9660, Vol. 25, No. 21
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.21.9646-9660.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»