Hedgehog pathway modulation by multiple lipid binding sites on the smoothened effector of signal response.
Hedgehog pathway modulation by multiple lipid binding sites on the smoothened effector of signal response.
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Hedgehog 通路通过信号响应平滑效应器上的多个脂质结合位点进行调节。
DOI：
10.1016/j.devcel.2013.07.015
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发表时间：
2013-08-26
影响因子：
11.8
通讯作者：
Beachy, Philip A.
中科院分区：
文献类型：
--
作者：
Myers, Benjamin R.;Sever, Navdar;Chong, Yong Chun;Kim, James;Belani, Jitendra D.;Rychnovsky, Scott;Bazan, J. Fernando;Beachy, Philip A.
Hedgehog (Hh) signaling during development and in postembryonic tissues requires activation of the 7TM oncoprotein Smoothened (Smo), by mechanisms that may involve endogenous lipidic modulators. Exogenous Smo ligands previously identified include the plant sterol cyclopamine (and its therapeutically useful synthetic mimics) and hydroxylated cholesterol derivatives (oxysterols); Smo is also highly sensitive to cellular sterol levels. The relationships between these effects are unclear because the relevant Smo structural determinants are unknown. We identify the conserved extracellular cysteine rich domain (CRD) as the site of action for oxysterols on Smo, involving residues structurally analogous to those contacting the Wnt lipid adduct in the homologous Frizzled CRD; this modulatory effect is distinct from that of cyclopamine mimics, from Hh-mediated regulation, and from the permissive action of cellular sterol pools. These results imply that Hh pathway activity is sensitive to lipid binding at several Smo sites, suggesting mechanisms for tuning by multiple physiological inputs.
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影响因子：
64.8
作者：
Bhanot, P;Brink, M;Nusse, R
通讯作者：
Nusse, R
影响因子：
6.5
作者：
Heo, Gun-Young;Bederman, Ilya;Pikuleva, Irina A.
通讯作者：
Pikuleva, Irina A.
影响因子：
64.5
作者：
Cadigan, KM;Fish, MP;Nusse, R
通讯作者：
Nusse, R
影响因子：
4.8
作者：
Benned-Jensen, Tau;Norn, Christoffer;Rosenkilde, Mette M.
通讯作者：
Rosenkilde, Mette M.
影响因子：
64.5
作者：
Denef, N;Neubüser, D;Cohen, SM
通讯作者：
Cohen, SM