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PMID: 9303540 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Dual pathways for induction of wingless expression by protein kinase A and Hedgehog in Drosophila embryos.

Genes & development ·Vol. 11 ·No. 17 ·1997-09-01 ·Pages 2250-8

Ohlmeyer JT, Kalderon D

Abstract

The secreted Drosophila Hedgehog (Hh) protein induces transcription of specific genes by an unknown mechanism that requires the serpentine transmembrane protein Smoothened (Smo) and the transcription factor Cubitus interruptus (Ci). Protein kinase A (PKA) has been implicated in the mechanism of Hh signal transduction because it acts to repress Hh target genes in imaginal disc cells that express Ci. Changes in Ci protein levels, detected by an antibody that recognizes an epitope in the carboxy-terminal half of Ci, have been suggested to mediate the positive effects of Hh and the negative effects of PKA on Hh target gene expression in imaginal discs. Here we show that PKA inhibition, like Hh, leads to increased "carboxy-terminal" Ci staining and Hh target gene expression in embryos. In addition, we find that Hh and Smo can stimulate target gene expression at constant Ci levels and that increased PKA activity can induce ectopic Hh target gene expression in a manner that requires Smo and Ci activities but does not involve changes in Ci protein concentration. This suggests a branching pathway of Hh signal transduction downstream of Smo and that PKA exerts opposite effects on the two branches. Finally we show that Hh signaling in embryos does not depend on cAMP-dependent regulation of PKA activity.

MeSH Terms
Animals Cyclic AMP/metabolism Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors,metabolism DNA-Binding Proteins/genetics,metabolism Drosophila/embryology,genetics,metabolism Drosophila Proteins Female Gene Expression Regulation, Developmental Genes, Insect Hedgehog Proteins In Situ Hybridization Insect Proteins/metabolism Male Proto-Oncogene Proteins/genetics Receptors, Cell Surface/genetics,metabolism Receptors, G-Protein-Coupled Signal Transduction Smoothened Receptor Transcription Factors Wnt1 Protein
Chemicals
DNA-Binding Proteins Drosophila Proteins Hedgehog Proteins Insect Proteins Proto-Oncogene Proteins Receptors, Cell Surface Receptors, G-Protein-Coupled Smoothened Receptor Transcription Factors Wnt1 Protein ci protein, Drosophila smo protein, Drosophila wg protein, Drosophila hh protein, Drosophila Cyclic AMP Cyclic AMP-Dependent Protein Kinases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Ohlmeyer J T
Department of Biological Sciences, Columbia University, New York 10027, USA.
Kalderon D
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.11.17.2250
Published
1997-09-01
Pages
2250-8
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC275396
Subset
IM
Grants
NIGMS NIH HHS · GM41815 · United States
External Links
PubMed source DOI: 10.1101/gad.11.17.2250 PMC Full Text View journal details
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