Extracellular tyrosyl-tRNA synthetase cleaved by plasma proteinases and stored in platelet α-granules: Potential role in monocyte activation.
Extracellular tyrosyl-tRNA synthetase cleaved by plasma proteinases and stored in platelet α-granules: Potential role in monocyte activation.
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血浆蛋白酶裂解并储存在血小板α颗粒中：单核细胞激活中的潜在作用。
DOI：
10.1002/rth2.12429
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发表时间：
2020-10
影响因子：
4.6
通讯作者：
Kanaji T
中科院分区：
文献类型：
--
作者：
Won E;Morodomi Y;Kanaji S;Shapiro R;Vo MN;Orje JN;Thornburg CD;Yang XL;Ruggeri ZM;Schimmel P;Kanaji T
酪氨酰-tRNA合成酶（YRS）属于催化蛋白质合成的tRNA氨酰化反应的酶家族，最近已被证明发挥非经典功能。尽管数据库结果表明血小板中YRS mRNA水平极低，但YRS蛋白大量存在。血小板中YRS的来源以及血小板储存YRS的生理作用在很大程度上仍然未知。为了阐明YRS如何在血小板中积累并确定血小板储存的YRS的潜在作用，制备了具有表位标签的重组YRS蛋白，并在体外检测了人血浆中的蛋白水解裂解。检查荧光标记的YRS是否被血小板摄取，如蛋白质印迹和共聚焦显微镜分析所示。使用RAW‐Dual报告细胞，在用YRS处理后分析Toll样受体和I型干扰素活化途径。全长YRS被血浆中的弹性蛋白酶和基质金属蛋白酶切割。切割的N末端YRS片段对应于通过蛋白质印迹法在血小板裂解物中检测到的内源性YRS。全长和裂解形式的YRS均在体外被血小板吸收并储存在α颗粒中。通过蛋白水解切割产生的N末端YRS片段具有与先前报道的组成型活性突变体YRS（YRSY 341 A）相当的单核细胞活化。血小板从血浆中摄取全长YRS和裂解的YRS片段的活性形式。储存在α颗粒中的切割的N末端YRS片段可能具有激活单核细胞的潜力。
Tyrosyl‐tRNA synthetase (YRS) belongs to the family of enzymes that catalyzes the tRNA aminoacylation reaction for protein synthesis, and it has been recently shown to exert noncanonical functions. Although database results indicate extremely low levels of YRS mRNA in platelets, YRS protein is abundantly present. The source of YRS in platelets, as well as the physiological role of platelet‐stored YRS, remains largely unknown. To clarify how YRS accumulates in platelets and determine the potential role of platelet‐stored YRS. Recombinant YRS proteins with epitope tags were prepared and tested in vitro for proteolytic cleavage in human plasma. Fluorescent‐labeled YRS was examined for uptake by platelets, as demonstrated by western blotting and confocal microscopy analysis. Using RAW‐Dual reporter cells, Toll‐like receptor and type I interferon activation pathways were analyzed after treatment with YRS. Full‐length YRS was cleaved by both elastase and matrix metalloproteinases in the plasma. The cleaved, N‐terminal YRS fragment corresponds to the endogenous YRS detected in platelet lysate by western blotting. Both full‐length and cleaved forms of YRS were taken up by platelets in vitro and stored in the α‐granules. The N‐terminal YRS fragment generated by proteolytic cleavage had monocyte activation comparable to that of the constitutive‐active mutant YRS (YRSY341A) previously reported. Platelets take up both full‐length YRS and the active form of cleaved YRS fragment from the plasma. The cleaved, N‐terminal YRS fragment stored in α‐granules may have potential to activate monocytes.
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影响因子：
64.8
作者：
Kim, Min-Sik;Pinto, Sneha M.;Getnet, Derese;Nirujogi, Raja Sekhar;Manda, Srikanth S.;Chaerkady, Raghothama;Madugundu, Anil K.;Kelkar, Dhanashree S.;Isserlin, Ruth;Jain, Shobhit;Thomas, Joji K.;Muthusamy, Babylakshmi;Leal-Rojas, Pamela;Kumar, Praveen;Sahasrabuddhe, Nandini A.;Balakrishnan, Lavanya;Advani, Jayshree;George, Bijesh;Renuse, Santosh;Selvan, Lakshmi Dhevi N.;Patil, Arun H.;Nanjappa, Vishalakshi;Radhakrishnan, Aneesha;Prasad, Samarjeet;Subbannayya, Tejaswini;Raju, Rajesh;Kumar, Manish;Sreenivasamurthy, Sreelakshmi K.;Marimuthu, Arivusudar;Sathe, Gajanan J.;Chavan, Sandip;Datta, Keshava K.;Subbannayya, Yashwanth;Sahu, Apeksha;Yelamanchi, Soujanya D.;Jayaram, Savita;Rajagopalan, Pavithra;Sharma, Jyoti;Murthy, Krishna R.;Syed, Nazia;Goel, Renu;Khan, Aafaque A.;Ahmad, Sartaj;Dey, Gourav;Mudgal, Keshav;Chatterjee, Aditi;Huang, Tai-Chung;Zhong, Jun;Wu, Xinyan;Shaw, Patrick G.;Freed, Donald;Zahari, Muhammad S.;Mukherjee, Kanchan K.;Shankar, Subramanian;Mahadevan, Anita;Lam, Henry;Mitchell, Christopher J.;Shankar, Susarla Krishna;Satishchandra, Parthasarathy;Schroeder, John T.;Sirdeshmukh, Ravi;Maitra, Anirban;Leach, Steven D.;Drake, Charles G.;Halushka, Marc K.;Prasad, T. S. Keshava;Hruban, Ralph H.;Kerr, Candace L.;Bader, Gary D.;Iacobuzio-Donahue, Christine A.;Gowda, Harsha;Pandey, Akhilesh
通讯作者：
Pandey, Akhilesh
影响因子：
14.8
作者：
Guo, Min;Schimmel, Paul
通讯作者：
Schimmel, Paul
影响因子：
4.4
作者：
Hottz, Eugenio D.;Medeiros-de-Moraes, Isabel M.;Bozza, Patricia T.
通讯作者：
Bozza, Patricia T.
影响因子：
8.8
作者：
Carestia, Agostina;Mena, Hebe A.;Schattner, Mirta
通讯作者：
Schattner, Mirta
DOI：
10.1016/s0735-1097(97)00510-x
发表时间：
1998-02-01
影响因子：
24
作者：
Furman, MI;Benoit, SE;Michelson, AD
通讯作者：
Michelson, AD