Canonical and Non-Canonical Hedgehog Signaling Pathways: Role of G Proteins

  • Natalia A. RioboEmail author
Part of the Topics in Medicinal Chemistry book series (TMC, volume 16)


The Hedgehog (Hh) signaling pathway has received a great deal of attention in the past decade due to its involvement in cancer, angiogenesis, and fibrosis. Several inhibitors of the pathway were developed which target the 7-transmembrane protein Smoothened (Smo), core component of the canonical pathway that controls Gli-dependent transcriptional activity. However, recent studies revealed that the Hh pathway has other transcription-independent functions, collectively known as “non-canonical signaling.” This review describes the role and function of each Hh pathway component in canonical and non-canonical signaling, with emphasis on the role of Smo as a GPCR that selectively activates heterotrimeric Gi proteins.


Gli Hedgehog Heterotrimeric G proteins Non-canonical Smoothened 



12 transmembrane








7 transmembrane


Adenosine monophosphate


3′-5′-cyclic adenosine monophosphate




Chromatin immunoprecipitation


Coenzyme A




(2-chloro-N-[4-chloro-3-pyridin-2-yl-phenyl]-4-methane-sulfonyl benzamide)


4-[[(1-Hexyl-1,2-dihydro-2-oxo-3-quinolinyl)carbonyl]amino]benzoic acid propyl ester




Guanosine 5′-O-[γ-thio]triphosphate








Nuclear export signal


Phosphatidylinositol 4-phosphate






Small interference RNA




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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Department of Biochemistry and Molecular Biology and Kimmel Cancer Center, Sidney Kimmel Medical CollegeThomas Jefferson UniversityPhiladelphiaUSA

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