TbetaRI/Alk5-independent TbetaRII signaling to ERK1/2 in human skin cells according to distinct levels of TbetaRII expression.
J Cell Sci
; 124(Pt 1): 19-24, 2011 Jan 01.
Article
em En
| MEDLINE
| ID: mdl-21172820
ABSTRACT
TGFß binding to the TGFß receptor (TßR) activates R-Smad-dependent pathways, such as Smad2/3, and R-Smad-independent pathways, such as ERK1/2. The mechanism of the TGFß-TßRII-TßRI-Smad2/3 pathway is established; however, it is not known how TGFß activates ERK1/2. We show here that although TGFß equally activated Smad2/3 in all cells, it selectively activated ERK1/2 in dermal cells and inhibited ERK1/2 in epidermal cells. These opposite effects correlated with the distinct expression levels of TßRII, which are 7- to 18-fold higher in dermal cells than in epidermal cells. Reduction of TßRII expression in dermal cells abolished TGFß-stimulated ERK1/2 activation. Upregulation of TßRII expression in epidermal cells to a similar level as that in dermal cells switched TGFß-induced ERK1/2 inhibition to ERK1/2 activation. More intriguingly, in contrast to the equal importance of TßRII in mediating TGFß signaling to both Smad2/3 and ERK1/2, knockdown of TßRI/Alk5 blocked activation of only Smad2/3, not ERK1/2, in dermal cells. Similarly, expression of the constitutively activated TßRI-TD kinase activated only Smad2/3 and not ERK1/2 in epidermal cells. This study provides an explanation for why TGFß selectively activates ERK1/2 in certain cell types and direct evidence for TßRI-independent TßRII signaling to a R-Smad-independent pathway.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Proteínas Serina-Treonina Quinases
/
Receptores de Fatores de Crescimento Transformadores beta
/
Proteína Quinase 1 Ativada por Mitógeno
/
Derme
/
Proteína Quinase 3 Ativada por Mitógeno
/
Epiderme
Limite:
Humans
Idioma:
En
Revista:
J Cell Sci
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos