Hedgehog patterning activity: Role of a lipophilic modification mediated by the carboxy-terminal autoprocessing domain

Jeffery A. Porter, Stephen C. Ekker, Woo Jin Park, Doris P. Von Kessler, Keith E. Young, Chien Huan Chen, Yong Ma, Amina S. Woods, Robert J. Cotter, Eugene V. Koonin, Philip A. Beachy

Research output: Contribution to journalArticlepeer-review

405 Scopus citations

Abstract

Autocatalytic processing mediated by the carboxyterminal domain of the hedgehog (hh) protein precursor (Hh) generates an amino-terminal product that accounts for all known signaling activity. The role of autoprocessing in biogenesis of the hh signal has been unclear, since a truncated unprocessed protein lacking all carboxy-terminal domain sequences retains signaling activity. Here, we present evidence that the autoprocessing reaction proceeds via an internal thioester intermediate and results in a covalent modification that increases the hydrophobic character of the signaling domain and influences its spatial and subcellular distribution. We demonstrate that truncated unprocessed amino-terminal protein causes embryonic mispatterning, even when expression is localized to cells that normally express Hh, thus suggesting a role for autoprocessing in spatial regulation of hh signaling. This type of processing also appears to operate in the biogenesis of other novel secreted proteins.

Original languageEnglish
Pages (from-to)21-34
Number of pages14
JournalCell
Volume86
Issue number1
DOIs
StatePublished - Jul 12 1996

Fingerprint Dive into the research topics of 'Hedgehog patterning activity: Role of a lipophilic modification mediated by the carboxy-terminal autoprocessing domain'. Together they form a unique fingerprint.

Cite this