Immune system dysfunction and autoimmune disease in mice lacking Emk (Par-1) protein kinase.
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.
Hurov
J B
JB
Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110-1093, USA.
Stappenbeck
T S
TS
Zmasek
C M
CM
White
L S
LS
Ranganath
S H
SH
Russell
J H
JH
Chan
A C
AC
Murphy
K M
KM
Piwnica-Worms
H
H
D000818:Animals; D001327:Autoimmune Diseases / Q000201:enzymology* / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000502:physiology; D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D003106:Colon / Q000002:abnormalities; D005260:Female; D015870:Gene Expression; D018390:Gene Targeting; D015432:Glomerulonephritis, Membranoproliferative / Q000201:enzymology; D006456:Hemoglobinuria / Q000201:enzymology; D006801:Humans; D007107:Immune System / Q000276:immunology; D008221:Lymphoid Tissue; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011391:Prolapse; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000276:immunology*; D011507:Proteinuria / Q000201:enzymology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000502:physiology
D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; C122043:Mark2 protein, mouse; D017346:Protein Serine-Threonine Kinases