title: ERK5 regulation in naïve T-cell activation and survival.
abstract: ERK5 has been implicated in regulating the MEF2-dependent genes Klf2 and nur77 downstream of the TCR and the maintenance of expression of CD62L on peripheral T cells. Based on this data, knockout of ERK5 would be predicted to compromise T-cell development and the maintenance of T cells in the periphery. Using an ERK5 conditional knockout, driven by CD4-CRE or Vav-CRE transgenes resulting in the loss of ERK5 in T cells, we have found that ERK5 is not required for T-cell development. In addition, normal numbers of T cells were found in the spleens and lymph nodes of these mice. We also find that TCR stimulation is not a strong signal for ERK5 activation in primary murine T cells. ERK5 was found to contribute to the induction of Klf2 but not nur77 mRNA following TCR activation. Despite the reduction in Klf2 mRNA, no effect was seen in ERK5 knockouts on either the mRNA levels for the Klf2 target genes CD62L, CCR7 and S1P, or the cell surface expression of CD62L. These results suggest that while ERK5 does contribute to Klf2 regulation in T cells, it is not essential for the expression of CD62L or T-cell survival.
authors.affiliation: MRC Protein Phosphorylation Unit, College of Life Sciences, Sir James Black Centre, University of Dundee, Dundee, UK.
authors.forename: Olga
authors.initials: O
authors.lastname: Ananieva
authors.forename: Andrew
authors.initials: A
authors.lastname: Macdonald
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Claire E
authors.initials: CE
authors.lastname: McCoy
authors.forename: Joanne
authors.initials: J
authors.lastname: McIlrath
authors.forename: Cathy
authors.initials: C
authors.lastname: Tournier
authors.forename: J Simon C
authors.initials: JS
authors.lastname: Arthur
mesh_terms: D000818:Animals; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D019041:L-Selectin / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D048054:Mitogen-Activated Protein Kinase 7 / Q000378:metabolism*; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D054400:Receptors, CCR7 / Q000378:metabolism; D049349:Receptors, Lysosphingolipid / Q000378:metabolism; D011987:Receptors, Steroid / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: C515371:Ccr7 protein, mouse; D004268:DNA-Binding Proteins; C498314:Klf2 protein, mouse; D051741:Kruppel-Like Transcription Factors; C539818:Nr4a1 protein, mouse; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D054400:Receptors, CCR7; D049349:Receptors, Lysosphingolipid; D011987:Receptors, Steroid; D019041:L-Selectin; D048054:Mitogen-Activated Protein Kinase 7