The tumour-suppressor gene patched encodes a candidate receptor for Sonic hedgehog

@article{Stone1996TheTG,
  title={The tumour-suppressor gene patched encodes a candidate receptor for Sonic hedgehog},
  author={Donna M. Stone and Mary Hynes and Mark P. Armanini and Todd A. Swanson and Qimin Gu and Ronald L. Johnson and Matthew P Scott and Diane Pennica and Audrey San Francisco Goddard and Heidi Phillips and Markus Noll and Joan E Hooper and Frederic j. de Sauvage and Arnon Rosenthal},
  journal={Nature},
  year={1996},
  volume={384},
  pages={129-134}
}
The protein Sonic hedgehog (Shh) controls patterning and growth during vertebrate development. Here we demonstrate that it binds Patched (vPtc), which has been identified as a tumour-suppressor protein in basal cell carcinoma, with high affinity. We show that Re can form a physical complex with a newly cloned vertebrate homologue of the Drosophila protein Smoothened (vSmo), and that vSmo is coexpressed with vPtc in many tissues but does not bind Shh directly. These findings, combined with… Expand
Expression of a sonic hedgehog signal transducer, hedgehog‐interacting protein, by human basal cell carcinoma
TLDR
This work has shown that hedgehog‐interacting protein (HIP) was found to bind to SHH directly and attenuate SHH signalling like PTC, while its expression was induced by SHH signals. Expand
Sonic hedgehog signaling by the Patched–Smoothened receptor complex
TLDR
It is demonstrated that Smo is the signaling component of a multicomponent Hh receptor complex and that Ptc is a ligand-regulated inhibitor of Smo. Expand
Characterization of two patched receptors for the vertebrate hedgehog protein family.
TLDR
Biochemical analysis of PTCH and PTCH2 shows that they both bind to all hedgehog family members with similar affinity and that they can form a complex with SMO, and Chromosomal localization ofPTCH2 places it on chromosome 1p33-34, a region deleted in some germ cell tumors, raising the possibility that PTCH 2 may be a tumor suppressor in Dhh target cells. Expand
Patched acts catalytically to suppress the activity of Smoothened
TLDR
It is reported that Ptc and Smo are not significantly associated within Hh-responsive cells and it is suggested that the Ptc tumour suppressor functions normally as a transmembrane molecular transporter, which acts indirectly to inhibit Smo activity, possibly through changes in distribution or concentration of a small molecule. Expand
Regional Distribution of Sonic Hedgehog, Patched, and Smoothened mRNA in the Adult Rat Brain
TLDR
The data suggest that, besides its roles in determining cell fate and patterning during embryogenesis, the hedgehog signaling pathway may have also important roles in the adult brain. Expand
The sonic hedgehog signaling network in development and neoplasia.
TLDR
The sonic hedgehog (SHH) pathway was first defined genetically in fruit flies and has been shown to be critical for normal mammalian development, by mediating interactions between stromal and epithelial cells. Expand
Expression of sonic hedgehog signal transducers, patched and smoothened, in human basal cell carcinoma
TLDR
It was found that the expressions of ptc and smo mRNA were enhanced in the tumor nests of the nodular BCC, especially at the advancing portions, but were under the detectable level in the superficial BCC cases examined, indicating that pTC and sme mRNA expressions might be associated with BCC tumor progression and divide the BCC histologic types into two subtypes, superficial and nodular types. Expand
In vivo evidence that Patched and Smoothened constitute distinct binding and transducing components of a Hedgehog receptor complex.
TLDR
The results suggest that Ptc normally binds Hh without any help from Smo and hence favor a mechanism of signal transduction in which Hh binds specifically to Ptc and induces a conformational change leading to the release of latent Smo activity. Expand
Genetic and biochemical definition of the Hedgehog receptor.
TLDR
It is concluded that Ihog and Ptc together constitute the Drosophila Hh receptor on the basis of their joint roles in ligand binding, signal transduction, and receptor trafficking. Expand
Sonic hedgehog in CNS development: one signal, multiple outputs
TLDR
A more precise understanding of the molecular mechanisms that underlie the different responses to SHH signalling is the next step in the study of this molecule and its role in the regulation of neural development. Expand
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TLDR
Three members of a mouse gene family related to the Drosophila segment polarity gene, hedgehog (hh), are identified and it is suggested that Shh may play a role in the normal inductive interactions that pattern the ventral CNS. Expand
The Drosophila smoothened Gene Encodes a Seven-Pass Membrane Protein, a Putative Receptor for the Hedgehog Signal
TLDR
It is suggested that smo encodes a receptor for the Hh signal, which is downstream of or in parallel to Patched, an antagonist of the HH signal. Expand
smoothened encodes a receptor-like serpentine protein required for hedgehog signalling
TLDR
It is shown that the segment-polarity gene smoothened is required for the response of cells to hedgehog signalling during the development of both the embryonic segments and imaginal discs. Expand
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TLDR
A mouse homolog of ptc is identified which in many tissues is transcribed near cells making either Sonic or Indian hedgehog, and ectopic Sonic hedgehog expression in the mouse central nervous system induces ptc transcription. Expand
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TLDR
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TLDR
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Human Homolog of patched, a Candidate Gene for the Basal Cell Nevus Syndrome
  • Ronald L. Johnson, Alana L. Rothman, +8 authors Matthew P. Scott
  • Biology, Medicine
  • Science
  • 1996
TLDR
Heritable mutations in BCNS patients and a somatic mutation in a sporadic BCC were identified in a human homolog of the Drosophila patched (ptc) gene, which appears to be crucial for proper embryonic development and for tumor suppression. Expand
Sonic hedgehog mediates the polarizing activity of the ZPA
TLDR
A vertebrate gene related to the Drosophila segment polarity gene hedgehog, which is expressed specifically in the ZPA and in other regions of the embryo, that is capable of polarizing limbs in grafting experiments is isolated. Expand
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