Smoothened adopts multiple active and inactive conformations capable of trafficking to the primary cilium.
Christopher W Wilson, Miao-Hsueh Chen, Pao-Tien Chuang
文献索引:PLoS ONE 4(4) , e5182, (2009)
全文:HTML全文
摘要
Activation of Hedgehog (Hh) signaling requires the transmembrane protein Smoothened (Smo), a member of the G-protein coupled receptor superfamily. In mammals, Smo translocates to the primary cilium upon binding of Hh ligands to their receptor, Patched (Ptch1), but it is unclear if ciliary trafficking of Smo is sufficient for pathway activation. Here, we demonstrate that cyclopamine and jervine, two structurally related inhibitors of Smo, force ciliary translocation of Smo. Treatment with SANT-1, an unrelated Smo antagonist, abrogates cyclopamine- and jervine-mediated Smo translocation. Further, activation of protein kinase A, either directly or through activation of Galphas, causes Smo to translocate to a proximal region of the primary cilium. We propose that Smo adopts multiple inactive and active conformations, which influence its localization and trafficking on the primary cilium.
相关化合物
相关文献:
2003-01-29
[J. Agric. Food Chem. 51(3) , 582-6, (2003)]
2013-04-15
[Exp. Cell Res. 319(7) , 1043-53, (2013)]
2000-01-01
[Acta Pharmacol. Sin. 21(1) , 23-8, (2000)]
2000-09-01
[Phytochemistry 55(1) , 19-22, (2000)]
2010-06-01
[Clin. Toxicol. (Phila.) 48(5) , 435-42, (2010)]