Cholesterol Modification of Hedgehog Signaling Proteins in Animal
Development
Jeffery A. Porter,
Keith E. Young,
Philip
A. Beachy
*
Hedgehog (Hh) proteins comprise a family of secreted signaling
molecules essential for patterning a variety of structures in animal
embryogenesis. During biosynthesis, Hh undergoes an autocleavage
reaction, mediated by its carboxyl-terminal domain, that produces a
lipid-modified amino-terminal fragment responsible for all known Hh
signaling activity. Here it is reported that cholesterol is the
lipophilic moiety covalently attached to the amino-terminal signaling
domain during autoprocessing and that the carboxyl-terminal domain acts
as an intramolecular cholesterol transferase. This use of cholesterol
to modify embryonic signaling proteins may account for some of the
effects of perturbed cholesterol biosynthesis on animal development.
Howard Hughes Medical Institute, Department of Molecular Biology
and Genetics, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
*
To whom correspondence should be addressed.
