In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 96, No. 20 ( 1999-09-28), p. 10992-10999
Abstract:
The amino-terminal signaling domain of the Sonic hedgehog secreted
protein (Shh-N), which derives from the Shh precursor through an autoprocessing reaction mediated by the carboxyl-terminal domain,
executes multiple functions in embryonic tissue patterning, including induction of ventral and suppression of dorsal cell types in the
developing neural tube. An apparent c atalytic site within Shh-N is
suggested by structural homology to a bacterial carboxypeptidase. We demonstrate here that alteration of residues presumed to be critical
for a hydrolytic activity does not cause a loss of inductive activity, thus ruling out catalysis by Shh-N as a requirement for signaling. We
favor the alternative, that Shh-N functions primarily as a ligand for the putative receptor Patched (Ptc). This possibility is supported by
new evidence for direct binding of Shh-N to Ptc and by a strong correlation between the affinity of Ptc-binding and the signaling
potency of Shh-N protein variants carrying alterations of conserved residues in a particular region of the protein surface. These results
together suggest that direct Shh-N binding to Ptc is a critical event in transduction of the Shh-N signal.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.96.20.10992
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
1999
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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