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PKAc-directed interaction and phosphorylation of Ptc is required for Hh signaling inhibition in Drosophila | |
2019-09-10 | |
发表期刊 | CELL DISCOVERY |
ISSN | 2056-5968 |
卷号 | 5 |
发表状态 | 已发表 |
DOI | 10.1038/s41421-019-0112-z |
摘要 | 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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收录类别 | SCI ; SCIE |
WOS研究方向 | Cell Biology |
WOS类目 | Cell Biology |
WOS记录号 | WOS:000487008500001 |
出版者 | NATURE PUBLISHING GROUP |
WOS关键词 | HIPPO PATHWAY ; HEDGEHOG ; MEMBRANE ; MEDULLOBLASTOMA ; PALMITOYLATION ; PROLIFERATION ; LOCALIZATION ; DYNAMICS |
原始文献类型 | Article |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/80232 |
专题 | 生命科学与技术学院_特聘教授组_赵允组 生命科学与技术学院_硕士生 |
通讯作者 | Chen, Dahua; Zhao, Yun |
作者单位 | 1.Univ Chinese Acad Sci, Chinese Acad Sci, Innovat Ctr Cell Signaling Network,Shanghai Inst, State Key Lab Cell Biol,CAS Ctr Excellence Mol Ce, Shanghai, Peoples R China 2.Chinese Acad Sci, Inst Zool, State Key Lab Membrane Biol, Beijing, Peoples R China 3.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China |
通讯作者单位 | 生命科学与技术学院 |
推荐引用方式 GB/T 7714 | Fan, Jialin,Gao, Yajie,Lu, Yi,et al. PKAc-directed interaction and phosphorylation of Ptc is required for Hh signaling inhibition in Drosophila[J]. CELL DISCOVERY,2019,5. |
APA | Fan, Jialin.,Gao, Yajie.,Lu, Yi.,Wu, Wenqing.,Yuan, Shuo.,...&Zhao, Yun.(2019).PKAc-directed interaction and phosphorylation of Ptc is required for Hh signaling inhibition in Drosophila.CELL DISCOVERY,5. |
MLA | Fan, Jialin,et al."PKAc-directed interaction and phosphorylation of Ptc is required for Hh signaling inhibition in Drosophila".CELL DISCOVERY 5(2019). |
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