Recombinant Drosophila melanogaster Protein smoothened (smo), partial

1. A novel mechanism for Smo activation by sumoylation that is regulated by Hh and Smo interacting proteins is uncovered. PMID: 28195188
2. Data show that Hedgehog (Hh) stimulates the binding of Smoothened (Smo) to a plasma membrane-associated kinase Gilgamesh (Gish)/CK1gamma and that Gish fine-tunes Hh pathway activity by phosphorylating a Ser/Thr cluster of Smo carboxyl-terminal intracellular tail (C-tail). PMID: 27280464
3. sumoylation acts in parallel with phosphorylation to promote Smo cell-surface expression and Hh signaling. PMID: 27746045
4. PI(4)P directly binds Smo through an arginine motif, which then triggers Smo phosphorylation and activation. PMID: 26863604
5. Smo protein can bias its signal and post-translational modification can impact this process. PMID: 26291458
6. Hedgehog-regulated atypical PKC promotes phosphorylation and activation of Smoothened and Cubitus interruptus in Drosophila. PMID: 25349414
7. Gprk2 phosphorylation in the membrane proximal C-terminus is an evolutionarily ancient mechanism of Smo regulation, and point to a higher degree of similarity in the regulation and signaling mechanisms of bilaterian Smo proteins PMID: 25009998
8. Hh induced a switch from the association of PKAc with a cytosolic complex of Ci and the kinesin-like protein Costal2 (Cos2) to a membrane-bound Smo-Cos2 complex. PMID: 24985345
9. findings demonstrate that deregulated Hedgehog signaling driven by active Smoothened mutants is attenuated by ER stressors that induce unfolded protein response (UPR); upon UPR induction, active Smoothened mutants are targeted by ER-associated degradation, resulting in attenuation of inappropriate pathway activity PMID: 23572559
10. Hh gradient signals, Smo transduces high level Hh signal by forming oligomers/higher order clusters in the lipid rafts of cell plasma membrane. PMID: 23532857
11. the differential phosphorylation of Smo mediates the thresholds of Hh activity PMID: 22537496
12. Results indicate that miR-5 can specifically suppress hedgehog (Hh) signaling by directly targeting smoothened (Smo) in Drosophila. PMID: 23085394
13. Hh-induced phosphorylation promotes Smo cell surface accumulation by inhibiting its ubiquitination, which contributes to Hh pathway activation. PMID: 22253574
14. These findings are consistent with loop cysteines engaging in disulfide bonds that facilitate a Smoothened conformation that is silent in the absence of Hedgehog, but can transition to a fully active state in response to ligand. PMID: 22223683
15. established a functional link between sequentially phosphorylated Smo species and graded Hh activity PMID: 21730325
16. Characterization of metabolic phenotypes in the medulloblastoma of smo transgenic mice. PMID: 20842126
17. Gprk2 promotes Smo activation by phosphorylating Smo C-terminal tail (C-tail) at Ser741/Thr742, which is facilitated by PKA and CK1 phosphorylation at adjacent Ser residues PMID: 20844016
18. results suggest a model in which Ptc directly or indirectly functions to suppress the accumulation of PI4P. Binding of Hh to Ptc derepresses the levels of PI4P, which, in turn, promotes Smo activation. PMID: 20643350
19. Patched normally regulates Smo degradation by changing the lipid composition of endosomes PMID: 19906846
20. These results provide insight into head morphogenesis and reveal an unexpected positive role for Ptc-Smo signaling in promoting cell proliferation. PMID: 11934850
21. Smo transduces the Hh signal by physically interacting with the Cos2/Fu protein complex. PMID: 14597665
22. Data show that a positive response of Costal2 to Hedgehog stimulation requires a portion of the Smoothened cytoplasmic tail and the Costal2 cargo domain, which interacts directly with Smoothened. PMID: 14636583
23. Smo mediates both inhibition of the endosome-associated Hedgehog signaling complex-repressor and activation of Hedgehog signaling complex-activated at the plasma membrane in response to Hh and through interaction with Cos2 PMID: 14645371
24. Smo protein requires the amino terminus and the juxtamembrane region of the carboxy terminus for normal activity and accumulates in the plasma membrane PMID: 15172682
25. Smoothened, similarly distributed to those regulating Ci, are essential for Smoothened to transduce a hedgehog signal and for normal regulation of Smoothened protein levels. PMID: 15592457
26. Smoothened is phosphorylated in Hedgehog pathway activation PMID: 15598741
27. Hh induces progressive Smo phosphorylation by PKA and CKI, leading to elevation of Smo cell-surface levels and signalling activity. PMID: 15616566
28. sm belongs to a family of heterogeneous nuclear ribonucleoprotein (hnRNP; it is proposed to control axonal navigation and connectivity which is partly achieved at the level of mRNA splicing or exporting. PMID: 15676023
29. Smoothened regulates activator and repressor functions of Hedgehog signaling via two distinct mechanisms PMID: 16423832
30. There is evidence of differences between Drosophila and vertebrates concerning signalling downstream of Smo, as well as in Smo itself. PMID: 16516476
31. Map kinase cytoplasmic hold is genetically dependent on Hedgehog and Decapentaplegic (Dpp) receptors Smo and Tkv. PMID: 16540506
32. the upstream part of the Hedgehog pathway involving Hedgehog interaction with Patched, regulation of Smoothened by Patched, and Smoothened enrichment at the plasma membrane is highly conserved between Drosophila and humans PMID: 16867986
33. The last 59 amino acids of Smoothened cytoplasmic tail directly bind the protein kinase Fused and negatively regulate the Hedgehog pathway. PMID: 17182028
34. Results show that Smoothened, Sex-lethal, and Patched co-immunoprecipitate and co-fractionate, suggesting a large complex of both membrane and cytoplasmic components of the Hedgehog pathway. PMID: 17284519
35. Hedgehog induced phosphorylation activates SMO by inducing a conformational switch PMID: 17960137
36. results demonstrate that Smo functions as a canonical GPCR, which signals through Galphai to regulate Hh pathway activation PMID: 18987629
37. Hh downregulates Smo-PP4 interaction that is mediated by Cos2. PMID: 19088085

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KEGG: dme:Dmel_CG11561

STRING: 7227.FBpp0077788

UniGene: Dm.244