A Global Phosphorylation Atlas of Proteins Within Pathological Site of Rotator Cuff Tendinopathy.
A Global Phosphorylation Atlas of Proteins Within Pathological Site of Rotator Cuff Tendinopathy.
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DOI：
10.3389/fmolb.2021.787008
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发表时间：
2021
影响因子：
5
通讯作者：
Cheng B
中科院分区：
文献类型：
--
作者：
Wang Y;Zhang J;Lin Y;Cheng S;Wang D;Rao M;Jiang Y;Huang X;Chen R;Xie Y;Yin P;Cheng B
肩袖肌腱病（RCT）是肩痛最常见的原因，因此提出了一个重要的临床问题。了解RCT的机制和生物化学变化将是至关重要的，并为在转化前景和临床实践中靶向新颖有效的治疗策略铺平道路。磷酸化修饰是蛋白质翻译后修饰的重要组成部分，与蛋白质的活性和功能调控密切相关。在这项研究中，我们在人类RCT患者的病理部位内生成了一个全球蛋白磷酸化图谱。通过使用串联质量标签（TMT）标记结合质谱，平均7，741个磷酸化位点（p-位点）和3，026个蛋白质被鉴定。与正常蛋白质相比，706个蛋白质中的1，668个p位点被鉴定为上调，而57个蛋白质中的73个p位点被下调。GO富集分析表明，大多数具有上调的P-位点的蛋白质在嗜中性粒细胞介导的免疫中起作用，而下调的P-位点主要参与肌肉发育。此外，通路分析发现NF-κ B相关的TNF信号通路和蛋白激酶C α（PKCα）相关的Wnt信号通路与RCT病理相关。最后，构建了一个加权的激酶位点磷酸化网络来识别潜在的核心激酶，其中丝氨酸/苏氨酸蛋白激酶39（serine/threonine-protein kinase 39，STLK 3）和哺乳动物STE 20样蛋白激酶1（mammalian STE 20-like protein kinase 1，MST 1）与Wnt通路的激活正相关。
Rotator cuff tendinopathy (RCT) is the most common cause of shoulder pain, therefore posing an important clinical problem. Understanding the mechanism and biochemical changes of RCT would be of crucial importance and pave the path to targeting novel and effective therapeutic strategies in translational perspectives and clinical practices. Phosphorylation, as one of the most important and well-studied post-translational modifications, is tightly associated with protein activity and protein functional regulation. Here in this study, we generated a global protein phosphorylation atlas within the pathological site of human RCT patients. By using Tandem Mass Tag (TMT) labeling combined with mass spectrometry, an average of 7,741 phosphorylation sites (p-sites) and 3,026 proteins were identified. Compared with their normal counterparts, 1,668 p-sites in 706 proteins were identified as upregulated, while 73 p-sites in 57 proteins were downregulated. GO enrichment analyses have shown that majority of proteins with upregulated p-sites functioned in neutrophil-mediated immunity whereas downregulated p-sites are mainly involved in muscle development. Furthermore, pathway analysis identified NF-κB–related TNF signaling pathway and protein kinase C alpha type (PKCα)–related Wnt signaling pathway were associated with RCT pathology. At last, a weighted kinase-site phosphorylation network was built to identify potentially core kinase, from which serine/threonine-protein kinase 39 (STLK3) and mammalian STE20-like protein kinase 1 (MST1) were proposed to be positively correlated with the activation of Wnt pathway.
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