Sonic hedgehog protein signals not as a hydrolytic enzyme but as an apparent ligand for Patched

Naoyuki Fuse, Tapan Maiti, Baolin Wang, Jeffery A. Porter, Traci M. Tanaka Hall, Daniel J. Leahy, Philip A. Beachy

Research output: Contribution to journalArticle

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 catalytic 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.

Original languageEnglish (US)
Pages (from-to)10992-10999
Number of pages8
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number20
DOIs
StatePublished - Sep 28 1999

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Hedgehog Proteins
Carboxypeptidases
Neural Tube
Catalysis
Catalytic Domain
Membrane Proteins
Ligands
Enzymes
Proteins
Patched Receptors

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Sonic hedgehog protein signals not as a hydrolytic enzyme but as an apparent ligand for Patched. / Fuse, Naoyuki; Maiti, Tapan; Wang, Baolin; Porter, Jeffery A.; Tanaka Hall, Traci M.; Leahy, Daniel J.; Beachy, Philip A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 96, No. 20, 28.09.1999, p. 10992-10999.

Research output: Contribution to journalArticle

Fuse, Naoyuki ; Maiti, Tapan ; Wang, Baolin ; Porter, Jeffery A. ; Tanaka Hall, Traci M. ; Leahy, Daniel J. ; Beachy, Philip A. / Sonic hedgehog protein signals not as a hydrolytic enzyme but as an apparent ligand for Patched. In: Proceedings of the National Academy of Sciences of the United States of America. 1999 ; Vol. 96, No. 20. pp. 10992-10999.
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AU - Tanaka Hall, Traci M.

AU - Leahy, Daniel J.

AU - Beachy, Philip A.

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