The ihog cell-surface proteins bind Hedgehog and mediate pathway activation.
The ihog gene (interference hedgehog), identified by RNA interference in Drosophila cultured cells, encodes a type 1 membrane protein shown here to bind and to mediate response to the active Hedgehog (Hh) protein signal. ihog mutations produce defects characteristic of Hh signaling loss in embryos and imaginal discs, and epistasis analysis places ihog action at or upstream of the negatively acting receptor component, Patched (Ptc). The first of two extracellular fibronectin type III (FNIII) domains of the Ihog protein mediates a specific interaction with Hh protein in vitro, but the second FNIII domain is additionally required for in vivo signaling activity and for Ihog-enhanced binding of Hh protein to cells coexpressing Ptc. Other members of the Ihog family, including Drosophila Boi and mammalian CDO and BOC, also interact with Hh ligands via a specific FNIII domain, thus identifying an evolutionarily conserved family of membrane proteins that function in Hh signal response.
Yao
Shenqin
S
Howard Hughes Medical Institute, Departments of Molecular Biology, Genetics, and Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Lum
Lawrence
L
Beachy
Philip
P
D000818:Animals; D019521:Body Patterning / Q000235:genetics; D002478:Cells, Cultured; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D004625:Embryo, Nonmammalian / Q000033:anatomy & histology / Q000502:physiology; D004628:Embryonic Structures / Q000033:anatomy & histology / Q000502:physiology; D005353:Fibronectins / Q000378:metabolism; D053823:Hedgehog Proteins; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011509:Proteoglycans / Q000378:metabolism; D034622:RNA Interference; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
D029721:Drosophila Proteins; D005353:Fibronectins; D053823:Hedgehog Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011509:Proteoglycans; D011956:Receptors, Cell Surface; D015534:Trans-Activators; C420997:dlp protein, Drosophila; C510880:iHog protein, Drosophila; C070844:ptc protein, Drosophila; C077245:hh protein, Drosophila