SEK1/MKK4 is required for maintenance of a normal peripheral lymphoid compartment but not for lymphocyte development.
SAPK is a member of the group of evolutionary conserved stress-activated kinases that mediate control of cellular death and proliferation. In lymphocytes, the SAPK pathway has been implicated in signaling from antigen, costimulatory, and death receptors; SEK1, which directly activates SAPK, is required for early embryonic development and has also been reported to be essential for normal lymphocyte development. In contrast to the latter findings, we have used RAG-2-deficient blastocyst complementation to show that SEK1-deficient embryonic stem cells support unimpaired T and B lymphocyte development. Moreover, mature SEK1-deficient lymphocytes are capable of SAPK activation. Surprisingly, however, aging SEK1-deficient chimeric mice frequently develop lymphadenopathy and polyclonal B and T cell expansions. Thus, SEK1 is not required for lymphocyte development, but is required for maintaining peripheral lymphoid homeostasis.
Swat
W
W
The Children's Hospital, The Center for Blood Research, Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Fujikawa
K
K
Ganiatsas
S
S
Yang
D
D
Xavier
R J
RJ
Harris
N L
NL
Davidson
L
L
Ferrini
R
R
Davis
R J
RJ
Labow
M A
MA
Flavell
R A
RA
Zon
L I
LI
Alt
F W
FW
D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology; D017252:CD3 Complex / Q000276:immunology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002451:Cell Compartmentation / Q000235:genetics*; D016922:Cellular Senescence; D002678:Chimera; D004789:Enzyme Activation; D006706:Homeostasis; D048031:JNK Mitogen-Activated Protein Kinases; D008214:Lymphocytes / Q000166:cytology*; D048670:MAP Kinase Kinase 4; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D011494:Protein Kinases / Q000235:genetics / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology; D019014:fas Receptor / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases
D017252:CD3 Complex; D019014:fas Receptor; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; C482562:Map2k4 protein, mouse; D020929:Mitogen-Activated Protein Kinase Kinases