Phosphoproteomics Analysis Reveals a Pivotal Mechanism Related to Amino Acid Signals in Goat Fetal Fibroblast.
Phosphoproteomics Analysis Reveals a Pivotal Mechanism Related to Amino Acid Signals in Goat Fetal Fibroblast.
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磷酸蛋白质组学分析揭示了与山羊胎儿成纤维细胞中氨基酸信号相关的关键机制。
DOI：
10.3389/fvets.2021.685548
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发表时间：
2021
影响因子：
3.2
通讯作者：
Wang Z
中科院分区：
文献类型：
--
作者：
Zheng X;Su H;Wang L;Yao R;Ma Y;Bai L;Wang Y;Guo X;Wang Z
除了作为蛋白质合成的基石，氨基酸还作为细胞中的关键信号分子。然而，氨基酸信号在细胞中被感知的机制尚未完全理解。本研究探讨了在蛋白质的磷酸化水平的差异，在绒山羊胎儿成纤维细胞（GFb）响应氨基酸信号。发现氨基酸缺乏诱导自噬并减弱GFb细胞中雷帕霉素复合物（mTORC 1）/Unc-51样自噬激活激酶1（ULK 1）信号传导的哺乳动物/机械靶标。使用基于磷酸化的蛋白质组学分析筛选了102个与氨基酸信号正相关的蛋白质上的共144个磷酸化位点。根据基因本体论（GO）和京都基因与基因组百科全书（KEGG）的分析，丝裂原活化蛋白激酶（MAPK）信号通路在参与氨基酸信号应答的相互作用网络中起着潜在的重要作用，而MAPK 1/3可能是整个网络的中心枢纽。基序分析确定了三个主基序，xxx_S_Pxx，xxx_S_xxE和xxx_S_xDx，它们集中在磷酸化受氨基酸信号正调控的磷酸化位点。此外，磷酸化水平的三个膜蛋白，锌转运蛋白SLC 39 A7，钠依赖性中性氨基酸转运蛋白SLC 1A 5和SLC 38 A7，和三个翻译起始因子，真核起始因子（eIF）5 B，eIF 4G，和eIF 3C，正调控的氨基酸信号。这些关键蛋白被添加到目前已知的信号通路中，以产生与氨基酸信号相关的网络通路的新模型。最后，通过蛋白质印迹分析检测响应于氨基酸信号的MAPK 3上的苏氨酸203和酪氨酸205的磷酸化水平，并且结果与来自磷酸蛋白质组学分析的数据一致。本研究的结果提供了新的证据和见解的精确机制，氨基酸信号的感知和进行在绒山羊胎儿成纤维细胞。
In addition to serving as the building blocks for protein synthesis, amino acids serve as critical signaling molecules in cells. However, the mechanism through which amino acid signals are sensed in cells is not yet fully understood. This study examined differences in the phosphorylation levels of proteins in response to amino acid signals in Cashmere goat fetal fibroblasts (GFb). Amino acid deficiency was found to induce autophagy and attenuate mammalian/mechanistic target of rapamycin complex (mTORC1)/Unc-51-like autophagy activating kinase 1 (ULK1) signaling in GFb cells. A total of 144 phosphosites on 102 proteins positively associated with amino acid signaling were screened using phosphorylation-based proteomics analysis. The mitogen-activated protein kinase (MAPK) signaling pathway was found to play a potentially important role in the interaction network involved in the response to amino acid signals, according to gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and MAPK1/3 may serve as a central hub for the entire network. Motif analysis identified three master motifs, xxx_S_Pxx, xxx_S_xxE, and xxx_S_xDx, which were centered on those phosphosites at which phosphorylation was positively regulated by amino acid signaling. Additionally, the phosphorylation levels of three membrane proteins, the zinc transporter SLC39A7, the sodium-dependent neutral amino acid transporters SLC1A5 and SLC38A7, and three translation initiation factors, eukaryotic initiation factor (eIF)5B, eIF4G, and eIF3C, were positively regulated by amino acid signals. These pivotal proteins were added to currently known signaling pathways to generate a novel model of the network pathways associated with amino acid signals. Finally, the phosphorylation levels of threonine 203 and tyrosine 205 on MAPK3 in response to amino acid signals were examined by western blot analysis, and the results were consistent with the data from the phosphoproteomics analysis. The findings of this study provide new evidence and insights into the precise mechanism through which amino acid signals are sensed and conducted in Cashmere goat fetal fibroblasts.
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