Gli protein activity is controlled by multisite phosphorylation in vertebrate Hedgehog signaling.
Gli protein activity is controlled by multisite phosphorylation in vertebrate Hedgehog signaling.
复制标题
DOI：
10.1016/j.celrep.2013.12.003
复制
发表时间：
2014-01-16
期刊：
影响因子：
8.8
通讯作者：
Rohatgi R
中科院分区：
文献类型：
--
作者：
Niewiadomski P;Kong JH;Ahrends R;Ma Y;Humke EW;Khan S;Teruel MN;Novitch BG;Rohatgi R
Gli蛋白是正常发育和癌症中Hedgehog（Hh）途径的转录效应物。我们描述了一个多位点磷酸化的程序，调节Gli蛋白转化为转录激活因子。在没有Hh配体的情况下，Gli活性受到蛋白激酶a（PKA）直接磷酸化6个保守丝氨酸残基的抑制，PKA是Hh途径的主要负调节剂。信号传导的激活导致Gli磷酸化景观的整体重塑：PKA靶位点变得去磷酸化，而第二簇位点经历磷酸化。Gli磷酸化的模式可以以分级的方式调节Gli转录活性，表明在形态发生场中Hh信号传导的梯度如何可以转化为转录活性的梯度的基于磷酸化的机制。
Gli proteins are transcriptional effectors of the Hedgehog (Hh) pathway in both normal development and cancer. We describe a program of multi-site phosphorylation that regulates the conversion of Gli proteins into transcriptional activators. In the absence of Hh ligands, Gli activity is restrained by the direct phosphorylation of six conserved serine residues by protein kinase a (PKA), a master negative regulator of the Hh pathway. Activation of signaling leads to a global remodeling of the Gli phosphorylation landscape: the PKA target sites become dephosphorylated, while a second cluster of sites undergoes phosphorylation. The pattern of Gli phosphorylation can regulate Gli transcriptional activity in a graded fashion, suggesting a phosphorylation based-mechanism for how a gradient of Hh signaling in a morphogenetic field can be converted into a gradient of transcriptional activity.
登录
查看更多内容
影响因子：
4.8
作者：
Niewiadomski, Pawel;Zhujiang, Annie;Waschek, James A.
通讯作者：
Waschek, James A.
影响因子：
30.8
作者：
Kang, S;Graham, JM;Biesecker, LG
通讯作者：
Biesecker, LG
影响因子：
4.6
作者：
Fuccillo, M;Rallu, M;Fishell, G
通讯作者：
Fishell, G
影响因子：
16.2
作者：
HYNES, M;PORTER, JA;ROSENTHAL, A
通讯作者：
ROSENTHAL, A
影响因子：
64.8
作者：
Corbit, KC;Aanstad, P;Reiter, JF
通讯作者：
Reiter, JF