Sonic hedgehog protein signals not as a hydrolytic enzyme but as an apparent ligand for patched. Academic Article uri icon

Overview

MeSH

  • Amino Acid Sequence
  • Cells, Cultured
  • Hedgehog Proteins
  • Heparin
  • Ligands
  • Molecular Sequence Data
  • Receptors, Cell Surface
  • Signal Transduction
  • Structure-Activity Relationship

MeSH Major

  • Hydrolases
  • Membrane Proteins
  • Proteins
  • Trans-Activators

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.

publication date

  • September 28, 1999

has subject area

  • Amino Acid Sequence
  • Cells, Cultured
  • Hedgehog Proteins
  • Heparin
  • Hydrolases
  • Ligands
  • Membrane Proteins
  • Molecular Sequence Data
  • Proteins
  • Receptors, Cell Surface
  • Signal Transduction
  • Structure-Activity Relationship
  • Trans-Activators

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC34231

PubMed ID

  • 10500113

Additional Document Info

start page

  • 10992

end page

  • 10999

volume

  • 96

number

  • 20