The Hedgehog (Hh) family of signaling molecules function as organizers in many morphogenetic processes. Hh signaling requires cholesterol in both signal-generating and -receiving cells, and it requires the tumor suppressor Patched (Ptc) in receiving cells in which it plays a negative role. Ptc both blocks the Hh pathway and limits the spread of Hh. Sequence analysis suggests that it has 12 tran...

Bone remodeling involves bone resorption by osteoclasts and synthesis by osteoblasts and is tightly regulated by the receptor activator of the NF-kappaB ligand (RANKL)/receptor activator of the NF-kappaB (RANK)/osteoprotegerin molecular triad. RANKL, a member of the TNF superfamily, induces osteoclast differentiation, activation and survival upon interaction with its receptor RANK. The decoy re...

Activation of hedgehog (HH) pathway signaling is observed in many tumors. Due to a feedback loop, the HH receptor Patched (PTCH-1) is overexpressed in tumors with activated HH signaling. Therefore, we sought to radiolabel the PTCH-1 ligand sonic (SHH) for detection of cancer cells with canonical HH activity. Receptor binding of ¹³¹I-SHH was increased in cell lines with high HH pathway activatio...

The receptor class Frizzled, which has recently been categorized as a separate group of G protein-coupled receptors by the International Union of Basic and Clinical Pharmacology, consists of 10 Frizzleds (FZD(1-10)) and Smoothened (SMO). The FZDs are activated by secreted lipoglycoproteins of the Wingless/Int-1 (WNT) family, whereas SMO is indirectly activated by the Hedgehog (HH) family of pro...

The Hedgehog (Hh) pathway was first defined by its role in segment polarity in the Drosophila melanogaster embryonic epidermis and has since been linked to many aspects of vertebrate development and disease. In humans, mutation of the Patched1 (PTCH1) gene, which encodes an inhibitor of Hh signaling, leads to tumors of the skin and pediatric brain. Despite the high level of conservation between...

Patched (Ptc) is a membrane protein whose function in Hedgehog (Hh) signal transduction has been conserved among metazoans and whose malfunction has been implicated in human cancers. Genetic analysis has shown that Ptc negatively regulates Hh signal transduction, but its activity and structure are not known. We investigated the functional and structural properties of Drosophila Ptc and its C-te...