title: Activation of a C-terminal transcriptional activation domain of ERK5 by autophosphorylation.
abstract: ERK5 plays a crucial role in many biological processes by regulating transcription. ERK5 has a large C-terminal-half that contains a transcriptional activation domain. However, it has remained unclear how its transcriptional activation activity is regulated. Here, we show that the activated kinase activity of ERK5 is required for the C-terminal-half to enhance the AP-1 activity, and that the activated ERK5 undergoes autophosphorylation on its most C-terminal region. Changing these phosphorylatable threonine and serine residues to unphosphorylatable alanines significantly reduces the transcriptional activation activity of ERK5. Moreover, phosphomimetic mutants of the C-terminal-half of ERK5 without an N-terminal kinase domain are shown to be able to enhance the AP-1 activity in fibroblastic cells. These results reveal the role of the stimulus-induced ERK5 autophosphorylation in regulation of gene expression.
authors.affiliation: Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Morimoto
authors.forename: Kunio
authors.initials: K
authors.lastname: Kondoh
authors.forename: Satoko
authors.initials: S
authors.lastname: Nishimoto
authors.forename: Kazuya
authors.initials: K
authors.lastname: Terasawa
authors.forename: Eisuke
authors.initials: E
authors.lastname: Nishida
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology*; D005786:Gene Expression Regulation / Q000502:physiology*; D051379:Mice; D048054:Mitogen-Activated Protein Kinase 7 / Q000235:genetics / Q000378:metabolism*; D020125:Mutation, Missense; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D017434:Protein Structure, Tertiary / Q000235:genetics; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D018808:Transcription Factor AP-1; D048054:Mitogen-Activated Protein Kinase 7