Letter abstract
Nature Cell Biology 7, 86 - 92 (2004)
Published online: 12 December 2004 | doi:10.1038/ncb1210
Drosophila Smoothened phosphorylation sites essential for Hedgehog signal transduction
Sergey Apionishev1, Natalya M. Katanayeva2, Steven A. Marks1, Daniel Kalderon1 & Andrew Tomlinson2
The Hedgehog (Hh) signalling pathway is crucial for animal development and is aberrantly activated in several types of cancer1. 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)2, 3. 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 Smoothened1, 4, which itself becomes hyperphosphorylated during Hh signalling5. 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.
- Department of Biological Sciences, Columbia University, 1212 Amsterdam Avenue, New York, NY 10027, USA.
- Department of Genetics and Development, Center for Neurobiology and Behavior, College of Physicians and Surgeons, Columbia University, 701 West 168th Street, New York, NY 10032, USA.
Correspondence to: Daniel Kalderon1 e-mail: ddk1@columbia.edu
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