Hedgehog signal transduction by Smoothened: Pharmacologic evidence for a 2-step activation process

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Hedgehog signal transduction by Smoothened: pharmacologic evidence for a 2-step activation process.

The Hedgehog (Hh) signaling pathway controls growth, cell fate decisions, and morphogenesis during development. Damage to Hh transduction machinery can lead to birth defects and cancer. The transmembrane protein Smoothened (Smo) relays the Hh signal and is an important drug target in cancer. Smo enrichment in primary cilia is thought to drive activation of target genes. Using small-molecule ago...

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Protein kinase A (PKA) silences the Hedgehog (Hh) pathway in Drosophila in the absence of ligand by phosphorylating the pathway's transcriptional effector, Cubitus interruptus (Ci). Smoothened (Smo) is essential for Hh signal transduction but loses activity if three specific PKA sites or adjacent PKA-primed casein kinase 1 (CK1) sites are replaced by alanine residues. Conversely, Smo becomes co...

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ژورنال

عنوان ژورنال: Proceedings of the National Academy of Sciences

سال: 2009

ISSN: 0027-8424,1091-6490

DOI: 10.1073/pnas.0813373106