Drosophila Smoothened phosphorylation sites essential for Hedgehog signal transduction.
Nat Cell Biol
; 7(1): 86-92, 2005 Jan.
Article
em En
| MEDLINE
| ID: mdl-15592457
ABSTRACT
The Hedgehog (Hh) signalling pathway is crucial for animal development and is aberrantly activated in several types of cancer. In Drosophila melanogaster, Hh signalling regulates target gene expression through the transcription factor Cubitus interruptus (Ci). Together, Protein Kinase A, Casein Kinase 1 and Glycogen Synthase Kinase 3 silence the pathway in the absence of ligand by phosphorylating Ci at a defined cluster of sites, thereby promoting its proteolytic conversion to a transcriptional repressor (Ci-75). In the presence of Hh, Ci-155 is no longer converted to Ci-75 and its ability to activate transcription is potentiated. All Hh responses require the seven transmembrane domain protein Smoothened, which itself becomes hyperphosphorylated during Hh signalling. Here we show that a cluster of protein kinase A and protein kinase A-primed casein kinase 1 phosphorylation sites in Smoothened, similarly distributed to those regulating Ci, are essential for Smoothened to transduce a Hh signal and for normal regulation of Smoothened protein levels.
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Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Proteínas de Drosophila
/
Receptores Acoplados a Proteínas G
/
Drosophila melanogaster
Limite:
Animals
Idioma:
En
Revista:
Nat Cell Biol
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Estados Unidos