title: Genetic insights into Map3k-dependent proliferative expansion of T cells.
abstract: Mapks are important regulators of T cell proliferative expansion and cell cycle progression. Detailed genetic analysis of unconventional iNKT cells in both Map3k1(ΔKD) and Lck(Cre/+)Map3k1(f/f) mice demonstrated that Mekk1 (encoded by Map3k1) signaling activates Mapks to regulate Cdkn1b (encoding p27(Kip1)) expression and p27(Kip1)-dependent proliferative expansion in response to antigen. Mekk1 signaling and activation of E3 ubiquitin ligase Itch, by a phosphorylation-dependent conformational change, is also an important regulatory mechanism for the control of T helper cell cytokine production. Cdkn1b expression is regulated by Mekk1-dependent signaling in differentiated Th17 cells. Mekk1 is one of the 19 Ste11-like Map3ks, and Mekk1 signaling regulates iNKT cell proliferative expansion in response to glycolipid antigens and T cell homeostasis in the liver. Tak1 (encoded by Map3k7), a related Map3k to Mekk1, similarly regulates the proliferative expansion and homeostasis of T cells in the liver, and this illustrates the importance of multiple Map3ks for mammalian Mapk signaling.
authors.affiliation: a Department of Medicine , Imperial College London , London , UK.
authors.forename: Tesha
authors.initials: T
authors.lastname: Suddason
authors.affiliation: a Department of Medicine , Imperial College London , London , UK.
authors.forename: Ewen
authors.initials: E
authors.lastname: Gallagher
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology / Q000378:metabolism; D008099:Liver / Q000166:cytology; D048728:MAP Kinase Kinase Kinase 1 / Q000378:metabolism; D020930:MAP Kinase Kinase Kinases / Q000235:genetics* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000235:genetics; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D013601:T-Lymphocytes / Q000166:cytology* / Q000201:enzymology*; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D050760:Cyclin-Dependent Kinase Inhibitor p27; D048728:MAP Kinase Kinase Kinase 1; D020930:MAP Kinase Kinase Kinases; D000099151:MAP Kinase Kinase Kinase 7
keywords: Cdkn1b; Mapk; Mekk1; T cell; iNKT; proliferation; th17