Switch of PKA substrates from Cubitus interruptus to Smoothened in the Hedgehog signalosome complex
| Autor: | Laurent Ruel, Pascal P. Thérond, Nadia Ranieri |
|---|---|
| Přispěvatelé: | Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA) |
| Rok vydání: | 2014 |
| Předmět: |
DNA
Complementary animal structures Blotting Western General Physics and Astronomy Models Biological General Biochemistry Genetics and Molecular Biology Receptors G-Protein-Coupled Substrate Specificity Animals Drosophila Proteins Immunoprecipitation Hedgehog Proteins Phosphorylation Protein kinase A [SDV.BDD]Life Sciences [q-bio]/Development Biology Hedgehog Transcription factor Multidisciplinary Chemistry General Chemistry Ci protein Anatomy Cyclic AMP-Dependent Protein Kinases Smoothened Receptor Cell biology DNA-Binding Proteins Hedgehog signalling Drosophila RNA Interference Smoothened Signal Transduction Transcription Factors |
| Zdroj: | Nature Communications Nature Communications, Nature Publishing Group, 2013, 5, pp.5034 |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/ncomms6034 |
| Popis: | International audience; Hedgehog (Hh) signalling is crucial for developmental patterning and tissue homeostasis. In Drosophila, Hh signalling is mediated by a bifunctional transcriptional mediator, called Cubitus interruptus (Ci). Protein Kinase A (PKA)-dependent phosphorylation of the serpentine protein Smoothened (Smo) leads to Ci activation, whereas PKA-dependent phosphorylation of Ci leads to the formation of Ci repressor form. The mechanism that switches PKA from an activator to a repressor is not known. Here we show that Hh signalling activation causes PKA to switch its substrates from Ci to Smo within the Hh signalling complex (HSC). In particular, Hh signalling increases the level of Smo, which then outcompetes Ci for association with PKA and causes a switch in PKA substrate recognition. We propose a new model in which the PKA is constitutively present and active within the HSC, and in which the relative levels of Ci and Smo within the HSC determine differential activation and cellular response to Hh signalling. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|