Open AccessNegative control of keratinocyte differentiation by Rho/CRIK signaling coupled with up-regulation of KyoT1/2 (FHL1) expression
Author(s) -
Maddalena Grossi,
Agnès HiouFeige,
Alice Tommasi di Vignano,
Enzo Calautti,
Paola Ostano,
Sam Lee,
Giovanna Chiorino,
G. Paolo Dotto
Publication year - 2005
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0505011102
Subject(s) - microbiology and biotechnology , rhoa , cellular differentiation , effector , lim domain , signal transduction , notch signaling pathway , rac gtp binding proteins , biology , cell adhesion , integrin , gtpase , small gtpase , regulation of gene expression , rac1 , cell , gene , transcription factor , genetics , zinc finger
Rho GTPases integrate control of cell structure and adhesion with downstream signaling events. In keratinocytes, RhoA is activated at early times of differentiation and plays an essential function in establishment of cell-cell adhesion. We report here that, surprisingly, Rho signaling suppresses downstream gene expression events associated with differentiation. Similar inhibitory effects are exerted by a specific Rho effector, CRIK (Citron kinase), which is selectively down-modulated with differentiation, thereby allowing the normal process to occur. The suppressing function of Rho/CRIK on differentiation is associated with induction of KyoT1/2, a LIM domain protein gene implicated in integrin-mediated processes and/or Notch signaling. Like activated Rho and CRIK, elevated KyoT1/2 expression suppresses differentiation. Thus, Rho signaling exerts an unexpectedly complex role in keratinocyte differentiation, which is coupled with induction of KyoT1/2, a LIM domain protein gene with a potentially important role in control of cell self renewal.