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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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