Negative control of keratinocyte differentiation by Rho/CRIK signaling coupled with up-regulation of KyoT1/2 (FHL1) expression.
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.
Grossi
Maddalena
M
Department of Biochemistry, Lausanne University, Epalinges, Vaud CH-1066, Switzerland.
Hiou-Feige
Agnès
A
Tommasi Di Vignano
Alice
A
Calautti
Enzo
E
Ostano
Paola
P
Lee
Sam
S
Chiorino
Giovanna
G
Dotto
G Paolo
GP
D000256:Adenoviridae; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D017931:DNA Primers; D005786:Gene Expression Regulation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D015603:Keratinocytes / Q000502:physiology*; D060588:LIM Domain Proteins; D051379:Mice; D046228:Microarray Analysis; D009124:Muscle Proteins / Q000378:metabolism*; D010957:Plasmids / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
D017931:DNA Primers; C486306:Fhl1 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D009124:Muscle Proteins; C115635:citron-kinase; D017346:Protein Serine-Threonine Kinases; D020742:rhoA GTP-Binding Protein