title: T-Cell-Specific Deletion of Map3k1 Reveals the Critical Role for Mekk1 and Jnks in Cdkn1b-Dependent Proliferative Expansion.
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).
authors.affiliation: Department of Medicine, Imperial College London, Du Cane Road, London W12 0NN, UK. Electronic address: teshas7@yahoo.com.
authors.forename: Tesha
authors.initials: T
authors.lastname: Suddason
authors.affiliation: Department of Medicine, Imperial College London, Du Cane Road, London W12 0NN, UK.
authors.forename: Saba
authors.initials: S
authors.lastname: Anwar
authors.affiliation: Department of Medicine, Imperial College London, Du Cane Road, London W12 0NN, UK.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Charlaftis
authors.affiliation: Department of Medicine, Imperial College London, Du Cane Road, London W12 0NN, UK. Electronic address: ewengallagher@outlook.com.
authors.forename: Ewen
authors.initials: E
authors.lastname: Gallagher
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism*; D005699:Galactosylceramides / Q000276:immunology / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D048728:MAP Kinase Kinase Kinase 1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D010766:Phosphorylation; D012313:RNA / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D054875:Ubiquitination
chemical_list: C493961:Cdkn1b protein, mouse; D005699:Galactosylceramides; C493154:alpha-galactosylceramide; D050760:Cyclin-Dependent Kinase Inhibitor p27; D012313:RNA; D048031:JNK Mitogen-Activated Protein Kinases; D048728:MAP Kinase Kinase Kinase 1; C482578:Map3k1 protein, mouse