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Cell Mol Life Sci. 2016 Apr;73(7):1317-32. doi: 10.1007/s00018-015-2127-4. Epub 2016 Jan 13.

Hedgehog signaling pathway: a novel model and molecular mechanisms of signal transduction.

Gorojankina T1,2,3,4,5.

Author information

1
Neuroscience Paris-Saclay Institute (Neuro-PSI), UMR 9197, CNRS, Université Paris-Sud, Bât. 32/33, CNRS, 91190, Gif-sur-Yvette, France. gorojankina@inaf.cnrs-gif.fr.
2
Institut Curie, Centre de Recherche, Orsay, France. gorojankina@inaf.cnrs-gif.fr.
3
CNRS UMR3347, 91400, Orsay, France. gorojankina@inaf.cnrs-gif.fr.
4
Univ. Paris Sud, Université Paris Saclay, Orsay, France. gorojankina@inaf.cnrs-gif.fr.
5
INSERM U1021, 91400, Orsay, France. gorojankina@inaf.cnrs-gif.fr.

Abstract

The Hedgehog (Hh) signaling pathway has numerous roles in the control of cell proliferation, tissue patterning and stem cell maintenance. In spite of intensive study, the mechanisms of Hh signal transduction are not completely understood. Here I review published data and present a novel model of vertebrate Hh signaling suggesting that Smoothened (Smo) functions as a G-protein-coupled receptor in cilia. This is the first model to propose molecular mechanisms for the major steps of Hh signaling, including inhibition of Smo by Patched, Smo activation, and signal transduction from active Smo to Gli transcription factors. It also suggests a novel role for the negative pathway regulators Sufu and PKA in these processes.

KEYWORDS:

7-DHC; Crosstalk; GPCR; Gli; Oxysterol; PKA; Patched; Primary cilium; Signal transduction; Smoothened; Sufu

PMID:
26762301
DOI:
10.1007/s00018-015-2127-4
[Indexed for MEDLINE]

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