TAILIEUCHUNG - Báo cáo sinh học: "Small-molecule modulators of Hedgehog signaling: identification and characterization of Smoothened agonists and antagonists."

Tuyển tập các báo cáo nghiên cứu về sinh học được đăng trên tạp chí sinh học Journal of Biology đề tài: Small-molecule modulators of Hedgehog signaling: identification and characterization of Smoothened agonists and antagonists. | J. Biol. Journal of Biology BioMed Central Research article Small-molecule modulators of Hedgehog signaling identification and characterization of Smoothened agonists and antagonists Maria Frank-Kamenetsky Xiaoyan M Zhang Steve Bottega Oivin Guicherit Hynek WichterleC Henryk Dudek David Bumcrot Frank Y Wang Simon Jones Janine Shulok Lee L Rubin and Jeffery A Porter Addresses Curis Inc. 61 Moulton Street Cambridge MA 02138 USA. Columbia University College of Physicians and Surgeons 701 West 168 Street New York NY 10032 USA. Correspondence Jeffery A Porter. E-mail jporter@ Published 6 November 2002 Journal of Biology 2002 1 10 The electronic version of this article is the complete one and can be found online at http content 1 2 10 2002 Frank-Kamenetsky et al. licensee BioMed Central Ltd ISSN 1475-4924 Received 23 July 2002 Revised 18 September 2002 Accepted 11 October 2002 Abstract Background The Hedgehog Hh signaling pathway is vital to animal development as it mediates the differentiation of multiple cell types during embryogenesis. In adults Hh signaling can be activated to facilitate tissue maintenance and repair. Moreover stimulation of the Hh pathway has shown therapeutic efficacy in models of Parkinson s disease and diabetic neuropathy. The underlying mechanisms of Hh signal transduction remain obscure however little is known about the communication between the pathway suppressor Patched Ptc a multipass transmembrane protein that directly binds Hh and the pathway activator Smoothened Smo a protein that is related to G-protein-coupled receptors and is capable of constitutive activation in the absence of Ptc. Results We have identified and characterized a synthetic non-peptidyl small molecule Hh-Ag that acts as an agonist of the Hh pathway. This Hh agonist promotes cell-type-specific proliferation and concentration-dependent differentiation in vitro while in utero it rescues aspects of the Hh-signaling defect in Sonic hedgehog-null but not .

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