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Am J Physiol Gastrointest Liver Physiol (January 31, 2008). doi:10.1152/ajpgi.00564.2007
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Submitted on December 4, 2007
Accepted on January 28, 2008

Hedgehog Processing and Biological Activity

Shohreh F Farzan1, Samer Singh1, Neal S Schilling1, and David J Robbins1*

1 Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire, United States

* To whom correspondence should be addressed. E-mail: david.j.robbins{at}dartmouth.edu.

The Hedgehog (Hh) family of secreted proteins is necessary for aspects of the development and maintenance of the gastrointestinal tract. Hh is thought to function as a morphogen, a mitogen, a cell survival factor and an axon guidance factor. Given its wide role in development, as well as in a variety of disease states, understanding the regulation of Hh function and activity is critically important. However, the study of Hh signaling has been impeded by its unusual biology. Hh is unique in that it is the only protein covalently modified by cholesterol, which in turn affects numerous aspects of its localization, release, movement and activity. All are important factors when considering Hh's physiological role, and animals have developed an intricate system of regulators, responsible for both promoting and inhibiting the activity of Hh. This review is intended to give a broad overview of how the biosynthesis and movement of Hh contributes to its biological activity.







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