Abstract
MAPK signaling is important for T lymphocyte development, homeostasis, and effector responses. To better understand the role of Mekk1 (encoded by Map3k1) in T cells, we conditionally deleted Map3k1 in Lck(Cre/+)Map3k1(f/f) mice, and these display larger iNKT cell populations within the liver, spleen, and bone marrow. Mekk1 signaling controls splenic and liver iNKT cell expansion in response to glycolipid antigen. Lck(Cre/+)Map3k1(f/f) mice have enhanced liver damage in response to glycolipid antigen. Mekk1 regulates Jnk activation in iNKT cells and binds and transfers Lys63-linked poly-ubiquitin onto Carma1. Map3k1 is critical for the regulation of p27(Kip1) (encoded by Cdkn1b).
Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Proliferation
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Cyclin-Dependent Kinase Inhibitor p27 / genetics
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Cyclin-Dependent Kinase Inhibitor p27 / metabolism*
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Galactosylceramides / immunology
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Galactosylceramides / pharmacology
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HEK293 Cells
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Humans
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JNK Mitogen-Activated Protein Kinases / metabolism*
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Liver / drug effects
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Liver / immunology
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Liver / metabolism
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Lymphocyte Activation / drug effects
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MAP Kinase Kinase Kinase 1 / deficiency
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MAP Kinase Kinase Kinase 1 / genetics
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MAP Kinase Kinase Kinase 1 / metabolism*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Natural Killer T-Cells / drug effects
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Natural Killer T-Cells / immunology
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Natural Killer T-Cells / metabolism*
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Phosphorylation
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RNA / metabolism
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Spleen / drug effects
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Spleen / immunology
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Spleen / metabolism
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Ubiquitination
Substances
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Cdkn1b protein, mouse
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Galactosylceramides
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alpha-galactosylceramide
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Cyclin-Dependent Kinase Inhibitor p27
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RNA
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JNK Mitogen-Activated Protein Kinases
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MAP Kinase Kinase Kinase 1
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Map3k1 protein, mouse