Evidence for a Novel Feedback Loop in the Hedgehog Pathway Involving Smoothened and Fused.
From: Laboratoire Génétique du Développement et Evolution, Institut Jacques Monod, Université Paris 7, Unité Mixte de Recherche 7592, Centre National de la Recherche Scientifique, Universités Paris 6 and 7, 2 Place Jussieu 75251 Paris, France.
Current biology : CB
- Publish Date: Aug 2007
- ISSN: 0960-9822
- Volume: 17
- Issue: 15
- Pages: 1326-33
- Medium: Print
- Language: English
- Citation (JAMA): Claret Sandra, Sanial Matthieu, Plessis Anne, et al. Evidence for a Novel Feedback Loop in the Hedgehog Pathway Involving Smoothened and Fused.. Curr. Biol. Aug 2007;17:1326-33
Abstract
Hedgehog (HH) is a major secreted morphogen involved in development, stem cell maintenance and oncogenesis [1, 2]. In Drosophila wing imaginal discs, HH produced in the posterior compartment diffuses into the anterior compartment to control target gene transcription via the transcription factor Cubitus interruptus (CI). The first steps in the reception and transduction of the HH signal are mediated by its receptor Patched (PTC) [3] and the seven-transmembrane-domain protein Smoothened (SMO) [4, 5]. PTC and HH control SMO by regulating its stability, trafficking, and phosphorylation (for review, see [6]). SMO interacts directly with the Ser-Thr protein kinase Fused (FU) and the kinesin-related protein Costal2 (COS2), which interact with each other and with CI in an intracellular Hedgehog transducing complex [7-9]. We show here that HH induces FU targeting to the plasma membrane in a SMO-dependent fashion and that, reciprocally, FU controls SMO stability and phosphorylation. FU anchorage to the membrane is sufficient to make it a potent SMO-dependent, PTC-resistant activator of the pathway. These findings reveal a novel positive-feedback loop in HH transduction and are consistent with a model in which FU and SMO, by mutually enhancing each other’s activities, sustain high levels of signaling and render the pathway robust to PTC level fluctuations.
Mesh Headings (Keywords): Animals, Drosophila, Drosophila Proteins, Hedgehog Proteins, Membrane Proteins, Phosphorylation, Protein-Serine-Threonine Kinases, Receptors, Cell Surface, Receptors, G-Protein-Coupled
Check for Full Text / PubMed Unique Identifier (PMID): 17658259
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.