Mutants of cubitus interruptus that are independent of PKA regulation are independent of hedgehog signaling.

Détails

ID Serval
serval:BIB_40D9818F742D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Mutants of cubitus interruptus that are independent of PKA regulation are independent of hedgehog signaling.
Périodique
Development
Auteur⸱e⸱s
Chen Y., Cardinaux J.R., Goodman R.H., Smolik S.M.
ISSN
0950-1991[print], 0950-1991[linking]
Statut éditorial
Publié
Date de publication
08/1999
Peer-reviewed
Oui
Volume
126
Numéro
16
Pages
3607-3616
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
Publication Status: ppublish
Résumé
Hedgehog (HH) is an important morphogen involved in pattern formation during Drosophila embryogenesis and disc development. cubitus interruptus (ci) encodes a transcription factor responsible for transducing the hh signal in the nucleus and activating hh target gene expression. Previous studies have shown that CI exists in two forms: a 75 kDa proteolytic repressor form and a 155 kDa activator form. The ratio of these forms, which is regulated positively by hh signaling and negatively by PKA activity, determines the on/off status of hh target gene expression. In this paper, we demonstrate that the exogenous expression of CI that is mutant for four consensus PKA sites [CI(m1-4)], causes ectopic expression of wingless (wg) in vivo and a phenotype consistent with wg overexpression. Expression of CI(m1-4), but not CI(wt), can rescue the hh mutant phenotype and restore wg expression in hh mutant embryos. When PKA activity is suppressed by expressing a dominant negative PKA mutant, the exogenous expression of CI(wt) results in overexpression of wg and lethality in embryogenesis, defects that are similar to those caused by the exogenous expression of CI(m1-4). In addition, we demonstrate that, in cell culture, the mutation of any one of the three serine-containing PKA sites abolishes the proteolytic processing of CI. We also show that PKA directly phosphorylates the four consensus phosphorylation sites in vitro. Taken together, our results suggest that positive hh and negative PKA regulation of wg gene expression converge on the regulation of CI phosphorylation.
Mots-clé
Animals, Animals, Genetically Modified, Binding Sites, Body Patterning, Consensus Sequence, Cyclic AMP-Dependent Protein Kinases/metabolism, DNA-Binding Proteins/chemistry, DNA-Binding Proteins/genetics, Drosophila Proteins, Drosophila melanogaster/embryology, Drosophila melanogaster/genetics, Hedgehog Proteins, Insect Proteins/genetics, Insect Proteins/physiology, Morphogenesis, Peptide Mapping, Phosphorylation, Signal Transduction, Transcription Factors, Transfection, Zinc Fingers
Pubmed
Web of science
Création de la notice
18/02/2008 10:32
Dernière modification de la notice
20/08/2019 13:39
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