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International Immunology Advance Access published online on June 14, 2006
International Immunology, doi:10.1093/intimm/dxl063
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© The Japanese Society for Immunology. 2006. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org
Received January 6, 2006
Accepted May 18, 2006

Article

ADAP is dispensable for NK cell development and function

Lindsey V. Fostel 1, Joanna Dluzniewska 2, Yoji Shimizu 3, Brandon J. Burbach 3, and Erik J. Peterson 1 *

1 Department of Internal Medicine, University of Minnesota Medical School, Center for Immunology, Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA
2 Department of Internal Medicine, University of Minnesota Medical School, Center for Immunology, Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Molecular Biology Unit, Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland
3 Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Center for Immunology, Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA

* To whom correspondence should be addressed.
Erik J. Peterson, E-mail: peter899{at}umn.edu


  Abstract

NK cells are key mediators of the innate immune response and anti-tumor surveillance. Adhesion and degranulation-promoting adapter protein (ADAP, formerly known as SLAP-130 or Fyb) is a hematopoietic-specific adapter that is required for efficient TCR signaling and T cell activation. Herein, we examine a potential role for ADAP in NK development and function. ADAP is expressed in primary NK cells and in IL-2 stimulated lymphokine-activated killers. However, ADAP-deficient mice show no defects in NK development. Further, ADAP is dispensable for key NK functions, including cytotoxicity in response to engagement of activating receptors, cytokine production, conjugate formation and tumor suppression in vivo. These results indicate that, unlike events stimulated by TCR engagement, signaling events engaged by immunoreceptor tyrosine-based activation motif-associated and cytokine receptors on NK cells can occur independently of ADAP.

Keywords: adaptor protein; adhesion and degranulation-promoting adapter protein; cytokine secretion; cytotoxicity; inhibitory signaling; Ly49 signaling; tumor suppression.
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B. J. Burbach, R. Srivastava, R. B. Medeiros, W. E. O'Gorman, E. J. Peterson, and Y. Shimizu
Distinct Regulation of Integrin-Dependent T Cell Conjugate Formation and NF-{kappa}B Activation by the Adapter Protein ADAP
J. Immunol., October 1, 2008; 181(7): 4840 - 4851.
[Abstract] [Full Text] [PDF]


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