Phosphorylation of TMEM55B by Erk/MAPK regulates lysosomal positioning.
Phosphorylation of TMEM55B by Erk/MAPK regulates lysosomal positioning.
复制标题
Erk/MAPK 磷酸化 TMEM55B 可调节溶酶体定位。
DOI：
10.1093/jb/mvz026
复制
发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Hazeki K.
中科院分区：
文献类型：
--
作者：
Takemasu S;Nigorikawa K;Yamada M;Tsurumi G;Kofuji S;Takasuga S;Hazeki K.
TMEM 55 B被首次鉴定为磷脂酰肌醇-4，5-P24-磷酸酶（PtdIns-4，5-P24-phosphatases），催化PtdIns-4，5-P24去磷酸化为PtdIns-5-P。RAW264.7巨噬细胞暴露于各种刺激诱导TMEM 55 B在Ser 76和Ser 169上的磷酸化，所述位点对应于用于通过MAPK磷酸化的共有序列（PX（S/T）P）。在这些刺激中，Toll样受体配体最强烈地诱导TMEM 55 B磷酸化，并且这被MEK 1/2抑制剂U 0126阻断。然而，磷酸化不影响TMEM 55 B的内在磷酸酶活性。TMEM 55 B最近被认为与饥饿诱导的溶酶体易位有关。氨基酸饥饿诱导RAW264.7巨噬细胞中的核周lamp 1聚集，其通过shRNA介导的敲除或CRISPR/Cas9介导的TMEM 55 B敲除而减弱。暴露于U 0126的细胞也表现出减弱的lamp 1聚集。TMEM 55 B而不是TMEM 55 A的过表达显著增强lamp 1聚类，其中TMEM 55 B突变体（缺乏磷酸化位点或模拟磷酸化状态）（分别）表现出比野生型TMEM 55 B更低和更高的功效。总的来说，结果表明TMEM 55 B通过Erk/MAPK的磷酸化影响溶酶体动力学。
TMEM55B is first identified as phosphatidylinositol-4,5-P24-phosphatases (PtdIns-4,5-P24-phosphatases) that catalyse dephosphorylation of PtdIns-4,5-P2to PtdIns-5-P. We demonstrate for the first time that TMEM55B is phosphorylated by Erk/MAPK and that this mechanism participates in regulation of lysosomal clustering. Exposure of RAW264.7 macrophages to various stimuli induces phosphorylation of TMEM55B on Ser76 and Ser169, sites corresponding to consensus sequences (PX(S/T)P) for phosphorylation by MAPK. Of these stimuli, Toll-like receptor ligands most strongly induce TMEM55B phosphorylation, and this is blocked by the MEK1/2 inhibitor U0126. However, phosphorylation does not impact intrinsic phosphatase activity of TMEM55B. TMEM55B has recently been implicated in starvation induced lysosomal translocation. Amino acid starvation induces perinuclear lamp1 clustering in RAW264.7 macrophages, which was attenuated by shRNA-mediated knock-down or CRISPR/Cas9-mediated knock-out of TMEM55B. Cells exposed to U0126 also exhibit attenuated lamp1 clustering. Overexpression of TMEM55B but not TMEM55A notably enhances lamp1 clustering, with TMEM55B mutants (lacking phosphorylation sites or mimicking the phosphorylated state) exhibiting lower and higher efficacies (respectively) than wild-type TMEM55B. Collectively, results suggest that phosphorylation of TMEM55B by Erk/MAPK impacts lysosomal dynamics.
登录
查看更多内容
抑制性受体 FcγRIIb 介导 IgG 对吞噬体酸化和包含 SHIP 和 Inpp4a 的连续去磷酸化系统的影响
影响因子：
3.2
作者：
Tomohiro Segawa;K. Hazeki;K. Nigorikawa;Atsuko Nukuda;Tomoki Tanizawa;K. Miyamoto;Shin Morioka;O. Hazeki
通讯作者：
O. Hazeki
DOI：
--
发表时间：
2014
期刊：
影响因子：
--
作者：
Tamotsu Yoshimori
通讯作者：
Tamotsu Yoshimori
Inpp5e 通过与 Rab20 相互作用，增加 Rab5 关联以及吞噬体中磷脂酰肌醇 3-磷酸的积累。
DOI：
10.1042/bj20140916
发表时间：
2014
期刊：
Biochem. J.
影响因子：
--
作者：
Segawa T;Hazeki K;Nigorikawa K;Morioka S;Guo Y;Takasuga S;Asanuma K;Hazeki O.
通讯作者：
Hazeki O.
影响因子：
11.8
作者：
Pu J;Schindler C;Jia R;Jarnik M;Backlund P;Bonifacino JS
通讯作者：
Bonifacino JS