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 HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Togni, M.
Right arrow Articles by Gerber, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Togni, M.
Right arrow Articles by Gerber, A.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, September 2005, p. 8052-8063, Vol. 25, No. 18
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.18.8052-8063.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Regulation of In Vitro and In Vivo Immune Functions by the Cytosolic Adaptor Protein SKAP-HOM

M. Togni,1,{dagger} K. D. Swanson,2,{dagger} S. Reimann,1 S. Kliche,1 A. C. Pearce,3 L. Simeoni,1 D. Reinhold,1 J. Wienands,4 B. G. Neel,2 B. Schraven,1* and A. Gerber1

Institute of Immunology, Otto von Guericke University, Magdeburg,1 Cellular and Molecular Immunology, Georg August University, Göttingen, Germany,4 Cancer Biology Program, Division of Hematology-Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts,2 Centre for Cardiovascular Sciences, Division of Medical Sciences, Institute of Biomedical Research, Wolfson Drive, The Medical School, University of Birmingham, Edgbaston, Birmingham, United Kingdom3

Received 24 March 2005/ Returned for modification 6 May 2005/ Accepted 17 June 2005

SKAP-HOM is a cytosolic adaptor protein representing a specific substrate for the Src family protein tyrosine kinase Fyn. Previously, several groups have provided experimental evidence that SKAP-HOM (most likely in cooperation with the cytosolic adaptor protein ADAP) is involved in regulating leukocyte adhesion. To further assess the physiological role of SKAP-HOM, we investigated the immune system of SKAP-HOM-deficient mice. Our data show that T-cell responses towards a variety of stimuli are unaffected in the absence of SKAP-HOM. Similarly, B-cell receptor (BCR)-mediated total tyrosine phosphorylation and phosphorylation of Erk, p38, and JNK, as well as immunoreceptor-mediated Ca2+ responses, are normal in SKAP-HOM–/– animals. However, despite apparently normal membrane-proximal signaling events, BCR-mediated proliferation is strongly attenuated in the absence of SKAP-HOM–/–. In addition, adhesion of activated B cells to fibronectin (a ligand for ß1 integrins) as well as to ICAM-1 (a ligand for ß2 integrins) is strongly reduced. In vivo, the loss of SKAP-HOM results in a less severe clinical course of experimental autoimmune encephalomyelitis following immunization of mice with the encephalitogenic peptide of MOG (myelin oligodendrocyte glycoprotein). This is accompanied by strongly reduced serum levels of MOG-specific antibodies and lower MOG-specific T-cell responses. In summary, our data suggest that SKAP-HOM is required for proper activation of the immune system, likely by regulating the cross-talk between immunoreceptors and integrins.

* Corresponding author. Mailing address: Institute of Immunology, Otto von Guericke University, Magdeburg, Leipziger Strasse 44, 39120 Magdeburg, Germany. Phone: 49 391 67 15800. Fax: 49 391 67 15852. E-mail: burkhart.schraven{at}medizin.uni-magdeburg.de.

{dagger} M. Togni and K. D. Swanson contributed equally to this work.

Molecular and Cellular Biology, September 2005, p. 8052-8063, Vol. 25, No. 18
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.18.8052-8063.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Reinhold, A., Reimann, S., Reinhold, D., Schraven, B., Togni, M. (2009). Expression of SKAP-HOM in DCs is required for an optimal immune response in vivo. J. Leukoc. Biol. 86: 61-71 [Abstract] [Full Text]  
  • Feng, C. Y., Johnson, S. C., Hori, T. S., Rise, M., Hall, J. R., Gamperl, A. K., Hubert, S., Kimball, J., Bowman, S., Rise, M. L. (2009). Identification and analysis of differentially expressed genes in immune tissues of Atlantic cod stimulated with formalin-killed, atypical Aeromonas salmonicida. Physiol. Genomics 37: 149-163 [Abstract] [Full Text]  
  • Burbach, B. J., Srivastava, R., Medeiros, R. B., O'Gorman, W. E., Peterson, E. J., Shimizu, Y. (2008). Distinct Regulation of Integrin-Dependent T Cell Conjugate Formation and NF-{kappa}B Activation by the Adapter Protein ADAP. J. Immunol. 181: 4840-4851 [Abstract] [Full Text]  
  • Arana, E., Harwood, N. E., Batista, F. D. (2008). Regulation of integrin activation through the B-cell receptor. J. Cell Sci. 121: 2279-2286 [Abstract] [Full Text]  
  • Missy, K., Hu, B., Schilling, K., Harenberg, A., Sakk, V., Kuchenbecker, K., Kutsche, K., Fischer, K.-D. (2008). {alpha}PIX Rho GTPase Guanine Nucleotide Exchange Factor Regulates Lymphocyte Functions and Antigen Receptor Signaling. Mol. Cell. Biol. 28: 3776-3789 [Abstract] [Full Text]  
  • Weber, M., Treanor, B., Depoil, D., Shinohara, H., Harwood, N. E., Hikida, M., Kurosaki, T., Batista, F. D. (2008). Phospholipase C-{gamma}2 and Vav cooperate within signaling microclusters to propagate B cell spreading in response to membrane-bound antigen. JEM 205: 853-868 [Abstract] [Full Text]  
  • Wang, H., Liu, H., Lu, Y., Lovatt, M., Wei, B., Rudd, C. E. (2007). Functional Defects of SKAP-55-Deficient T Cells Identify a Regulatory Role for the Adaptor in LFA-1 Adhesion. Mol. Cell. Biol. 27: 6863-6875 [Abstract] [Full Text]  
  • Kasirer-Friede, A., Moran, B., Nagrampa-Orje, J., Swanson, K., Ruggeri, Z. M., Schraven, B., Neel, B. G., Koretzky, G., Shattil, S. J. (2007). ADAP is required for normal {alpha}IIb{beta}3 activation by VWF/GP Ib-IX-V and other agonists. Blood 109: 1018-1025 [Abstract] [Full Text]  
  • Kliche, S., Breitling, D., Togni, M., Pusch, R., Heuer, K., Wang, X., Freund, C., Kasirer-Friede, A., Menasche, G., Koretzky, G. A., Schraven, B. (2006). The ADAP/SKAP55 Signaling Module Regulates T-Cell Receptor-Mediated Integrin Activation through Plasma Membrane Targeting of Rap1.. Mol. Cell. Biol. 26: 7130-7144 [Abstract] [Full Text]  
  • Kolsch, U., Arndt, B., Reinhold, D., Lindquist, J. A., Juling, N., Kliche, S., Pfeffer, K., Bruyns, E., Schraven, B., Simeoni, L. (2006). Normal T-Cell Development and Immune Functions in TRIM-Deficient Mice.. Mol. Cell. Biol. 26: 3639-3648 [Abstract] [Full Text]  


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