PKAc-directed interaction and phosphorylation of Ptc is required for Hh signaling inhibition in Drosophila
PKAc-directed interaction and phosphorylation of Ptc is required for Hh signaling inhibition in Drosophila
复制标题
果蝇中 Hh 信号传导抑制需要 PKAc 引导的相互作用和 Ptc 磷酸化
DOI：
10.1038/s41421-019-0112-z
复制
发表时间：
2019-09
期刊：
影响因子：
33.5
通讯作者：
Yun Zhao
中科院分区：
文献类型：
--
作者：
Jialin Fan;Yajie Gao;Yi Lu;Wenqing Wu;Shuo Yuan;Hailong Wu;Dahua Chen;Yun Zhao
Ptc是避免异常Hh信号激活的守门人，但参与Ptc介导的抑制的关键调节因子在很大程度上仍然未知。在这里，我们确定pdac是Ptc抑制功能所需的关键调节因子。在Hh缺失的情况下，ppkac与Ptc发生物理相互作用，使Ptc的Ser-1150和-1183位点磷酸化。Hh的存在从Ptc中释放pac并激活Hh信号。通过结合体外和体内功能分析，我们证明Ptc - ppkac相互作用和Ptc磷酸化对Ptc抑制功能都很重要。有趣的是，我们进一步证明ppkac受到棕榈酰化，有助于其在质膜上的激酶活性。基于这些新发现，我们建立了Ptc抑制功能的工作模型：在Hh缺失的情况下，ppkac与Ptc相互作用并磷酸化Ptc以确保其抑制功能；Hh的存在释放Ptc中的pac，导致Hh信号激活。
Ptc is a gatekeeper to avoid abnormal Hh signaling activation, but the key regulators involved in Ptc-mediated inhibition remain largely unknown. Here, we identify PKAc as a key regulator required for Ptc inhibitory function. In the absence of Hh, PKAc physically interacts with Ptc and phosphorylates Ptc at Ser-1150 and -1183 residues. The presence of Hh unleashes PKAc from Ptc and activates Hh signaling. By combining both in vitro and in vivo functional assays, we demonstrate that such Ptc–PKAc interaction and Ptc phosphorylation are both important for Ptc inhibitory function. Interestingly, we further demonstrate that PKAc is subjected to palmitoylation, contributing to its kinase activity on plasma membrane. Based on those novel findings, we establish a working model on Ptc inhibitory function: In the absence of Hh, PKAc interacts with and phosphorylates Ptc to ensure its inhibitory function; and Hh presence releases PKAc from Ptc, resulting in Hh signaling activation.
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DOI：
10.1016/j.bbamcr.2013.02.022
发表时间：
2013-06
影响因子：
5.1
作者：
De Napoli, M. G.;de Miguel, N.;Lebrun, M.;Moreno, S. N. J.;Angel, S. O.;Corvi, M. M.
通讯作者：
Corvi, M. M.
影响因子：
11.8
作者：
Zhao Zhang;Xiangdong Lv;Wen-chi Yin;Xiaoyun Zhang;Jing Feng;Wenqing Wu;C. Hui;Lei Zhang;
通讯作者：
Zhao Zhang;Xiangdong Lv;Wen-chi Yin;Xiaoyun Zhang;Jing Feng;Wenqing Wu;C. Hui;Lei Zhang;
影响因子：
64.8
作者：
Qi X;Schmiege P;Coutavas E;Wang J;Li X
通讯作者：
Li X
影响因子：
9.8
作者：
Li S;Chen Y;Shi Q;Yue T;Wang B;Jiang J
通讯作者：
Jiang J
影响因子：
48
作者：
Wisniewski, Jacek R.;Zougman, Alexandre;Mann, Matthias
通讯作者：
Mann, Matthias