title: TGF-beta activates ERK5 in human renal epithelial cells.
abstract: The role of the MAP kinase, extracellular signal-regulated kinase 5 (ERK5) remains unknown, however it is involved in cell differentiation and survival as highlighted by the embryonic lethality of the ERK5 knockout. ERK5 can be activated by growth factors and other extracellular signals. TGF-beta, a powerful controller of epithelial cell phenotype, is known to activate the MAP kinase, ERK1/2 however its effect on ERK5 remains unknown. This study demonstrates, fort the first time, ERK5 activation by TGF-beta, observed in both transformed and primary adult human PTEC; activation required ALK-5 receptor activity. In addition this work demonstrates expression of myocyte enhancer factor-2 (MEF2C) by PTEC and that TGF-beta increased the association of MEK5 with phospho-ERK5 and MEF2C. ERK5 activation by either TGF-beta or epidermal growth factor (EGF) was also inhibited by the p38 MAP kinase inhibitor, SB-202190.
authors.affiliation: South West Thames Institute for Renal Research, St. Helier Hospital, Carshalton, Surrey SM5 1AA, UK. james.browne@epsom-sthelier.nhs.uk
authors.forename: James Alexander
authors.initials: JA
authors.lastname: Browne
authors.forename: Alexander L
authors.initials: AL
authors.lastname: Pearson
authors.forename: Riad Abou
authors.initials: RA
authors.lastname: Zahr
authors.forename: Ioana
authors.initials: I
authors.lastname: Niculescu-Duvaz
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Baines
authors.forename: Mark E C
authors.initials: ME
authors.lastname: Dockrell
mesh_terms: D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007668:Kidney / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D026161:MADS Domain Proteins / Q000378:metabolism*; D064326:MEF2 Transcription Factors; D048054:Mitogen-Activated Protein Kinase 7 / Q000378:metabolism*; D018006:Myogenic Regulatory Factors / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases; D011725:Pyridines / Q000494:pharmacology; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000819:agonists; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
chemical_list: D007093:Imidazoles; D026161:MADS Domain Proteins; D064326:MEF2 Transcription Factors; C578040:MEF2C protein, human; D018006:Myogenic Regulatory Factors; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D048054:Mitogen-Activated Protein Kinase 7; D048051:p38 Mitogen-Activated Protein Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625841:TGFBR1 protein, human; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole