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Molecular and Cellular Biology, May 2001, p. 3206-3219, Vol. 21, No. 9
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.9.3206-3219.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Immune System Dysfunction and Autoimmune Disease in Mice Lacking Emk (Par-1) Protein Kinase

Jonathan B. Hurov,1 Thaddeus S. Stappenbeck,2,3 Christian M. Zmasek,4 Lynn S. White,1,5 Sheila H. Ranganath,3 John H. Russell,2 Andrew C. Chan,3,5,6 Kenneth M. Murphy,3,5 and Helen Piwnica-Worms1,5,*

Department of Cell Biology and Physiology,1 Department of Molecular Biology and Pharmacology,2 Department of Pathology and Immunology,3 Department of Genetics,4 Howard Hughes Medical Institute,5 and Department of Medicine,6 Washington University School of Medicine, St. Louis, Missouri 63110-1093

Received 22 November 2000/Returned for modification 3 January 2001/Accepted 26 January 2001

Emk is a serine/threonine protein kinase implicated in regulating polarity, cell cycle progression, and microtubule dynamics. To delineate the role of Emk in development and adult tissues, mice lacking Emk were generated by targeted gene disruption. Emk-/- mice displayed growth retardation and immune cell dysfunction. Although B- and T-cell development were normal, CD4+T cells lacking Emk exhibited a marked upregulation of the memory marker CD44/pgp-1 and produced more gamma interferon and interleukin-4 on stimulation through the T-cell receptor in vitro. In addition, B-cell responses to T-cell-dependent and -independent antigen challenge were altered in vivo. As Emk-/- animals aged, they developed splenomegaly, lymphadenopathy, membranoproliferative glomerulonephritis, and lymphocytic infiltrates in the lungs, parotid glands and kidneys. Taken together, these results demonstrate that the Emk protein kinase is essential for maintaining immune system homeostasis and that loss of Emk may contribute to autoimmune disease in mammals.

* Corresponding author. Mailing address: Department of Cell Biology and Physiology, Washington University School of Medicine, Box 8228, 660 South Euclid Ave., St. Louis, MO 63110. Phone: (314) 362-6812. Fax: (314) 362-3709. E-mail: hpiwnica{at}cellbio.wustl.edu.

Molecular and Cellular Biology, May 2001, p. 3206-3219, Vol. 21, No. 9
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.9.3206-3219.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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