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Cited by 381Hedgehog Signaling Pathway StudiesWnt/β-catenin signaling in development and cancerHippo pathway signaling and YAP/TAZ

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Proteolysis of the Hedgehog Signaling Effector Cubitus interruptus Requires Phosphorylation by Glycogen Synthase Kinase 3 and Casein Kinase 1

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Price, Mary Ann, Kalderon, Daniel·2002·Cell
DOI 10.1016/s0092-8674(02)00664-5
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Abstract

The secreted signaling molecule Hedgehog regulates gene expression in target cells in part by preventing proteolysis of the full-length Cubitus interruptus (Ci-155) transcriptional activator to the Ci-75 repressor form. Ci-155 proteolysis depends on phosphorylation at three sites by Protein Kinase A (PKA). We show that these phosphoserines prime further phosphorylation at adjacent Glycogen Synthase Kinase 3 (GSK3) and Casein Kinase I (CK1) sites. Alteration of the GSK3 or CK1 sites prevents Ci-155 proteolysis and activates Ci in the absence of Hedgehog. Ci-155 proteolysis is also inhibited if cells lack activity of the Drosophila GSK3, Shaggy, previously implicated in Wingless signaling. Conversely, Ci-155 levels are reduced in Hedgehog-responding cells by overexpression of PKA and the Drosophila CK1, Double-time, a regulator of circadian rhythms.

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Metadata

Authors
Price, M. A., & Kalderon, D.
Affiliations
Columbia University (US)
Corresponding author
Kalderon, Daniel
ORCID
Kalderon, Daniel
Venue
Cell
Publisher
Elsevier BV
Published
2002-03
Volume
108
Issue
6
Pages
823-835
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/s0092-8674(02)00664-5
OpenAlex
W2168256871
Cited by
381
References
54
Citations by year
2026: 2 · 2025: 5 · 2024: 2 · 2023: 5 · 2022: 12 · 2021: 17 · 2020: 16 · 2019: 9 · 2018: 9 · 2017: 12 · 2016: 12 · 2015: 12 · 2014: 20 · 2013: 21 · 2012: 15
FWCI
11.35
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of General Medical Sciences (R01GM041815, GM-41815)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Hedgehog Signaling Pathway Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
Keywords
Hedgehog signaling, Cubitus interruptus, proteolysis, glycogen synthase kinase-3, casein kinase 1, Shaggy, double time, protein kinase A, phosphorylation, transcriptional activator, Drosophila, Wingless signaling, circadian rhythm
MeSH terms
Amino Acid Sequence, Animals, Binding Sites, DNA-Binding Proteins, Drosophila, Molecular Sequence Data, Mutation, Phosphorylation, Protein Kinases, Proto-Oncogene Proteins, Transcription Factors, Signal Transduction, Gene Expression Regulation, Enzymologic, Protein Serine-Threonine Kinases, Cyclic AMP-Dependent Protein Kinases, Calcium-Calmodulin-Dependent Protein Kinases, Drosophila Proteins, Zebrafish Proteins, Glycogen Synthase Kinases, Glycogen Synthase Kinase 3, Casein Kinases, Wnt Proteins, Hedgehog Proteins, In Vitro Techniques

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