title: Rac, PAK and p38 regulate cell contact-dependent nuclear translocation of myocardin-related transcription factor.
abstract: We investigated the mechanism whereby cell contact injury stimulates the alpha-smooth muscle actin (SMA) promoter, a key process for epithelial-mesenchymal transition (EMT) during organ fibrosis. Contact disruption by low-Ca(2+) medium (LCM) activated Rac, PAK and p38 MAPK, and triggered the nuclear accumulation of myocardin-related transcription factor (MRTF), an inducer of the SMA promoter. Dominant negative (DN) Rac, DN-PAK, DN-p38, or the p38 inhibitor SB203580 suppressed the LCM-induced nuclear accumulation of MRTF and the activation of the SMA promoter. These studies define novel pathway(s) involving Rac, PAK, and p38 in the regulation of MRTF and the contact-dependent induction of EMT.
authors.affiliation: Keenan Research Centre, Li Ka Shing Knowledge Institute of St. Michael's Hospital, 30 Bond Street, Toronto, Ontario, Canada.
authors.forename: Attila
authors.initials: A
authors.lastname: Sebe
authors.forename: András
authors.initials: A
authors.lastname: Masszi
authors.forename: Matthew
authors.initials: M
authors.lastname: Zulys
authors.forename: Tony
authors.initials: T
authors.lastname: Yeung
authors.forename: Pam
authors.initials: P
authors.lastname: Speight
authors.forename: Ori D
authors.initials: OD
authors.lastname: Rotstein
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Nakano
authors.forename: István
authors.initials: I
authors.lastname: Mucsi
authors.forename: Katalin
authors.initials: K
authors.lastname: Szászi
authors.forename: András
authors.initials: A
authors.lastname: Kapus
mesh_terms: D000818:Animals; D018374:LLC-PK1 Cells; D008856:Microscopy, Fluorescence; D009687:Nuclear Proteins / Q000502:physiology*; D010766:Phosphorylation; D021381:Protein Transport; D013552:Swine; D015534:Trans-Activators / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*; D054462:p21-Activated Kinases / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology*; D020744:rac GTP-Binding Proteins / Q000502:physiology*; D000099251:Myocardin
chemical_list: D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D054462:p21-Activated Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020744:rac GTP-Binding Proteins; D000099251:Myocardin