Structure of the human smoothened receptor bound to an antitumour agent. [PDF]
Nature, 2013 The smoothened (SMO) receptor, a key signal transducer in the Hedgehog (Hh) signaling pathway is both responsible for the maintenance of normal embryonic development and implicated in carcinogenesis. The SMO receptor is classified as a class Frizzled (class F) G protein-coupled receptor (GPCR), although the canonical Hh signaling pathway involves the ...
Wang C +9 more
europepmc +7 more sources
A structurally guided dissection-then-evolution strategy for ligand optimization of smoothened receptor. [PDF]
Medchemcomm, 2017 We present herein a novel dissection-then-evolution strategy for ligand optimization.
Ye L +12 more
europepmc +5 more sources
A Smoothened receptor agonist is neuroprotective and promotes regeneration after ischemic brain injury. [PDF]
Cell Death Dis, 2014 Ischemic stroke occurs as a result of blood supply interruption to the brain causing tissue degeneration, patient disabilities or death. Currently, treatment of ischemic stroke is limited to thrombolytic therapy with a narrow time window of ...
Chechneva OV +6 more
europepmc +7 more sources
Structural basis for Smoothened receptor modulation and chemoresistance to anticancer drugs. [PDF]
Nat Commun, 2014 The Smoothened receptor (SMO) mediates signal transduction in the hedgehog pathway, which is implicated in normal development and carcinogenesis. SMO antagonists can suppress the growth of some tumors; however, mutations at SMO have been found to abolish their anti-tumor effects, a phenomenon known as chemoresistance.
Wang C +13 more
europepmc +5 more sources
Elucidation of Distinct Modular Assemblies of Smoothened Receptor by Bitopic Ligand Measurement. [PDF]
Journal of Medicinal Chemistry, 2021 Class F G protein-coupled receptors are characterized by a large extracellular domain (ECD) in addition to the common transmembrane domain (TMD) with seven α-helixes.
F. Zhao +16 more
semanticscholar +3 more sources
Nilotinib, an approved leukemia drug, inhibits smoothened signaling in Hedgehog-dependent medulloblastoma. [PDF]
PLoS ONE, 2019 Dysregulation of the seven-transmembrane (7TM) receptor Smoothened (SMO) and other components of the Hedgehog (Hh) signaling pathway contributes to the development of cancers including basal cell carcinoma (BCC) and medulloblastoma (MB).
Kirti Kandhwal Chahal +7 more
doaj +2 more sources
Cholesterol activates the G-protein coupled receptor Smoothened to promote Hedgehog signaling
eLife, 2016 Cholesterol is necessary for the function of many G-protein coupled receptors (GPCRs). We find that cholesterol is not just necessary but also sufficient to activate signaling by the Hedgehog (Hh) pathway, a prominent cell-cell communication system in ...
Giovanni Luchetti +8 more
doaj +5 more sources
E3 ubiquitin ligase Wwp1 regulates ciliary dynamics of the Hedgehog receptor Smoothened
Journal of Cell Biology, 2021 At the basal state, the ciliary levels of Smo are kept low through the actions of a ciliary localized E2 ubiquitin–conjugating enzyme, Ube2l3, and an E3 ubiquitin ligase, Wwp1.
Bo Lv +4 more
semanticscholar +4 more sources
Regulation of Smoothened by Drosophila G-protein-coupled receptor kinases
Developmental Biology, 2010 The Hedgehog (Hh) signaling pathway plays a conserved and essential role in regulating development and homeostasis of numerous tissues. Cytoplasmic signaling is initiated by Smoothened (Smo), a G-protein-coupled receptor (GPCR) family member, whose levels and activity are regulated by the Hh receptor Patched (Ptc). In response to Hh binding to Ptc, Ptc-
Cheng, Shuofei +3 more
openaire +4 more sources
The Development of a High-Content Screening Binding Assay for the Smoothened Receptor [PDF]
SLAS Discovery, 2012 In this study, the development of an image-based high-content screening (HCS) binding assay for the seven-transmembrane (7TM) receptor Smoothened (Smo) is described.
W. T. Bee +11 more
semanticscholar +3 more sources