Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Sci. Signal., 22 November 2011
Vol. 4, Issue 200, p. pt7
[DOI: 10.1126/scisignal.2002396]

PRESENTATIONS

Sonic Hedgehog Activates the GTPases Rac1 and RhoA in a Gli-Independent Manner Through Coupling of Smoothened to Gi Proteins

Ariel H. Polizio1, Pilar Chinchilla1, Xiaolen Chen1, David R. Manning2, and Natalia A. Riobo1,3*

1 Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
2 Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
3 Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.

A Presentation from the 1st International HEALING Meeting: Hh-Gli Signaling in Development, Regeneration and Disease, Kolymbari, Crete, 23 to 25 June 2011.

Abstract: The vertebrate Hedgehog (Hh) pathway has essential functions during development and tissue homeostasis in normal physiology, and its dysregulation is a common theme in cancer. The Hh ligands (Sonic Hh, Indian Hh, and Desert Hh) bind to the receptors Patched1 and Patched2, resulting in inhibition of their repressive effect on Smoothened (Smo). Smo is a seven-transmembrane protein, which was only recently shown to function as a G protein–coupled receptor (GPCR) with specificity toward the heterotrimeric guanine nucleotide-binding protein Gi. In addition to activating Gi, Smo signals through its C-terminal tail to inhibit Suppressor of Fused, resulting in stabilization and activation of the Gli family of transcription factors, which execute a transcriptional response to so-called "canonical Hh signaling." In this Presentation, we illustrate two outcomes of Hh signaling that are independent of Gli transcriptional activity and, thus, are defined as "noncanonical." One outcome is dependent on Smo coupling to Gi proteins and exerts changes to the actin cytoskeleton through stimulation of the small guanosine triphosphatases (GTPases) RhoA and Rac1. These cytoskeletal changes promote migration in fibroblasts and tubulogenesis in endothelial cells. Signaling through the other noncanonical Hh pathway is independent of Smo and inhibits Patched1-induced cell death.

* Presenter and corresponding author. E-mail: natalia.riobo{at}jefferson.edu

Citation: A. H. Polizio, P. Chinchilla, X. Chen, D. R. Manning, N. A. Riobo, Sonic Hedgehog Activates the GTPases Rac1 and RhoA in a Gli-Independent Manner Through Coupling of Smoothened to Gi Proteins. Sci. Signal. 4, pt7 (2011).

Read the Full Text

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Smoothened Oligomerization/Higher Order Clustering in Lipid Rafts Is Essential for High Hedgehog Activity Transduction.
D. Shi, X. Lv, Z. Zhang, X. Yang, Z. Zhou, L. Zhang, and Y. Zhao (2013)
J. Biol. Chem. 288, 12605-12614
   Abstract »    Full Text »    PDF »
The transition from differentiation to growth during dermomyotome-derived myogenesis depends on temporally restricted hedgehog signaling.
N. Kahane, V. Ribes, A. Kicheva, J. Briscoe, and C. Kalcheim (2013)
Development 140, 1740-1750
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882