The tumour-suppressor gene patched encodes a candidate receptor for Sonic hedgehog.
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 Ptc 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 available genetic evidence from Drosophila, support the hypothesis that Ptc is a receptor for Shh, and that vSmo could be a signalling component that is linked to Ptc.
Department of Neuroscience, Genentech, Inc., South San Francisco, California 94080, USA.
D M
DM
Stone
M
M
Hynes
M
M
Armanini
T A
TA
Swanson
Q
Q
Gu
R L
RL
Johnson
M P
MP
Scott
D
D
Pennica
A
A
Goddard
H
H
Phillips
M
M
Noll
J E
JE
Hooper
F
F
de Sauvage
A
A
Rosenthal
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002460:Cell Line; D003001:Cloning, Molecular; D004330:Drosophila; D029721:Drosophila Proteins; D016147:Genes, Tumor Suppressor; D053823:Hedgehog Proteins; D006801:Humans; D007301:Insect Hormones / Q000235:genetics* / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D017386:Sequence Homology, Amino Acid; D000072086:Smoothened Receptor; D014018:Tissue Distribution; D015534:Trans-Activators
D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D007301:Insect Hormones; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011506:Proteins; C000606240:Ptch1 protein, mouse; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C509239:SHH protein, human; C491023:SMO protein, human; C491022:Smo protein, mouse; D000072086:Smoothened Receptor; D015534:Trans-Activators; C070844:ptc protein, Drosophila; C100664:smo protein, Drosophila