Recombinant Mouse Smoothened homolog (Smo)

1. Identify SMO-dependent Shh signalling as a specific process for the activation of adventitial fibroblasts and the subsequent proliferation of smooth muscle cells and neointima formation. PMID: 29088375
2. cholesterol within the bilayer is sufficient for constitutive Smoothened activation. Cholesterol effects occur independently of the lipid-binding Smoothened extracellular domain, a region that is dispensable for Patched1-Smoothened coupling. PMID: 29229834
3. Highest levels of vertebrate Hedgehog signaling activity require efficient Smo ciliary enrichment. PMID: 29571613
4. This study showed for the first time that sustained Smo inhibits postnatal kidney development by suppressing the proliferation of the mesenchyme and medullary collecting ducts in mice. PMID: 28564646
5. the cytosolic phospholipase cPLA2alpha is activated through Gbetagamma downstream of Smo to release arachidonic acid. Arachidonic acid binds Smo and synergizes with CRD-binding agonists, promoting Smo ciliary trafficking and high-level signaling. PMID: 28591579
6. The s find that cholesterol, an important component of the cell membrane, directly binds to Smoothened and changes its shape so that it can activate Hedgehog signaling components inside cells. PMID: 27705744
7. Depletion of SMO mRNA in Jurkat cells facilitated HIV-1 vector infection, suggesting that endogenous SMO plays a role in limiting lentiviral infection. These results suggest that SMO inhibits HIV-1 replication after completion of reverse transcription but before integration. PMID: 28917838
8. These findings support a model in which Ptch1/2 mediate secretion of a Smo-inhibitory cholesterol precursor. PMID: 27552050
9. the data suggest that CCRK positively regulates the kinetics by which ciliary proteins such as Smoothened and Gli2 are imported into the cilium, and that the efficiency of ciliary recruitment allows for potent responses to Hedgehog signaling over long time periods. PMID: 28817564
10. SMO is covalently modified by cholesterol. This modification is regulated by Ptch1 and Hh and is essential for Hh signaling. PMID: 28344083
11. Downregulation of Smo activity, using selective Smo inhibitor cyclopamine, lead to a synergistic effect with TMP, whereas Smo overexpression plasmid impaired the induction of antiangiogenesic effects of TMP. PMID: 28112475
12. A screen for analogs revealed another six molecules, with IC50 values in the low micromolar range. Importantly, one of the most active of the new antagonists continued to be efficacious at the D473H mutant of Smoothened, which confers clinical resistance to the antagonist vismodegib in cancer treatment. PMID: 27490099
13. disruption of paracrine Hedgehog signaling via genetic ablation of Smoothened (Smo) in stromal fibroblasts in a Kras(G12D) mouse model increased acinar-to-ductal metaplasia PMID: 27633013
14. Collectively, these findings suggest that Smo and primary cilia-dependent noncanonical Hh signaling leads to post-translational regulation of microtubules and may be important for modulating cell behaviors. PMID: 27793670
15. The Hedgehog pathway receptor SMO is an important regulator of gastric cancer paclitaxel resistance. PMID: 28350784
16. these findings identify several compounds with the potential to treat drug-resistant SmoM2-driven cancer forms, but also reveal off-target effects of established drugs in the clinics PMID: 26931153
17. SMO overexpression leads to increased susceptibility to kainate excitotoxicity and seizure, in the cerebral cortex of Dach-SMO mice through the appearance of a glutamate-releasing response to kainate from astrocyte processes due to activation of Ca(2+)-permeable AMPA receptors. PMID: 26530396
18. exogenous addition of 3beta,5alpha-dihydroxycholest-7-en-6-one, a naturally occurring B-ring oxysterol derived from 7-DHC that also accumulates in Smith-Lemli-Opitz syndrome, blocked Hedgehog signaling by inhibiting activation of the essential transduction component Smoothened, through a mechanism distinct from Smoothened modulation by other lipids. PMID: 27162362
19. Data show the effects of genetic loss of ephrin-A5, Eph receptors EphA4, and EphA7 on the development of medulloblastoma tumors in the smoothened (Smo) transgenic mouse model. PMID: 26345456
20. Data show that halcinonide and clobetasol act as Smoothened (Smo) agonists to up-regulate myelin gene expression and retinoid X receptor gamma (RxRgamma) activation. PMID: 26658258
21. Genetic evidence for a Smoothened-Galpha(i) signaling axis in mammals. PMID: 26373671
22. findings show that activated SMO functions as a GPCR to stimulate proliferation in vivo PMID: 26373672
23. Data show that the Hedgehog (Hh) pathway activation by either a ligand or genetic loss of the negatively acting Hh receptor Patched-1 (Ptch) reduced the affinity and frequency of signaling protein Smoothened (Smo) binding at the base. PMID: 26100903
24. Increased expression of Smo activates breast cancer stem-like cells and promotes tumorigenesis. PMID: 25451166
25. These data identify Notch signalling as a novel modulator of Shh signalling that acts mechanistically via regulation of ciliary localisation of key components of its transduction machinery. PMID: 25995356
26. The Hedgehog pathway with its member Smoothened is required during a discrete embryonic period (E9.5-E12.5) in lens development to regulate lens epithelial cell proliferation, survival and FoxE3 expression. PMID: 25268479
27. Data indicate that the bromodomain protein inhibitor I-BET151 attenuates Hedgehog signaling downstream of Smoothened protein. PMID: 25355313
28. a bifurcation of Smo activity in Hh response, with a Dlg5-independent arm for suppression of Gli repressor formation and a second arm involving Smo interaction with Dlg5 for Gli activation PMID: 25644602
29. Suggest a novel miR-326-negative feedback loop in regulating the activity of Shh/Gli/Smo signaling. PMID: 24617895
30. Hrs mediates Smo trafficking in the late endosome by not only promoting Smo ubiquitination but also blocking Smo phosphorylation. PMID: 24244405
31. The results depicted pancytopenic feature of peripheral blood, developmental anomaly of neutrophils, depression of primitive stem and progenitor population along with Shh, Ptch1, Smo and Gli1 expression in aplasia group PMID: 23152377
32. Smo interacts with ILK and is required for SHh-driven activation of Gli2 in the embryonic mouse cerebellum. PMID: 23877428
33. Our data suggest that Smoothened signaling, acting through cyclin D2, is critical for the proper development and maturation of the neocortex. PMID: 23680462
34. These results highlight previously unrecognized effects of Shh-Smoothened signaling in the region-specific neurogenesis within the ventral midbrain PMID: 23618354
35. Hedgehog pathway activity is sensitive to lipid binding at several Smo sites, suggesting mechanisms for tuning by multiple physiological inputs. PMID: 23954590
36. results show that oxysterol binding to vertebrate Smo is required for normal Hh signaling and that targeting the oxysterol-binding site is an effective strategy to inhibit Smo PMID: 23831757
37. SMO is a master regulator of hepatic epithelial regeneration based on its ability to promote mesenchymal-to-epithelial transitions in a subpopulation of stellate cell-derived myofibrblasts. PMID: 23563311
38. Sustained Smo activation inhibits postnatal development of bone by suppressing gene expression of bone formation regulatory factors in mice. PMID: 22983747
39. sustained SMO up-regulation may contribute to T-cell lymphoblastic lymphoma development and the use of specific SMO inhibitors or microRNAs-based therapies as an attractive possibility to treat an important subset of T-cell lymphoblastic lymphomas PMID: 23288923
40. Smo translocation to the cilium was normal in Evc2-deficient chondrocytes following Hh activation with the Smo-agonist SAG PMID: 23026747
41. data suggest that the Smo-Evc2 signaling complex at the EvC zone is required for Hh signal transmission and elucidate the molecular basis of two human ciliopathies PMID: 22981989
42. Data indicate that STAT3 knockout reduces SmoM2-mediated carcinogenesis. PMID: 22992748
43. Studies suggest that altered subcellular localization of the transducer Smoothened, which functions in both the canonical and noncanonical pathways, is responsible for eliciting distinct Hedgehog (Hh) outputs. PMID: 22912492
44. Data indicate that smoothened (Smo) mutants unable to localize to the primary cilium preferentially mediate Hedgehog (Hh) chemotaxis. . PMID: 22912493
45. It was shown how two nearly contiguous point mutations in the same domain of the encoded Smoothened protein can produce striking phenotypic differences in cerebellar development and organization in mice. PMID: 22869526
46. different pools of Smo move into cilia through distinct mechanisms PMID: 22864913
47. Smo mRNA was expressed in the face of embryos at 11 and 12.5 days post coitum (dpc). After 13.5 dpc, the expression decreased to a low level and was faintly detected after birth. PMID: 21859383
48. Inhibition of hedgehog signalling exerted potent antifibrotic effects in preclinical models of SSc in both preventive and therapeutic settings. PMID: 22402139
49. our findings show that inhibition of the Hh pathway can reduce tumor burden, regardless of tumor Hh responsiveness, through effects on tumor cells, OCs, and stromal cells within the tumor microenvironment. PMID: 22186138
50. Arl13b regulates the ciliary entry of Smo. PMID: 21976698

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KEGG: mmu:319757

STRING: 10090.ENSMUSP00000001812

UniGene: Mm.29279