| http://purl.uniprot.org/citations/31771979 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/31771979 | http://www.w3.org/2000/01/rdf-schema#comment | "Tyrosyl-tRNA synthetase ligates tyrosine to its cognate tRNA in the cytoplasm, but it can also be secreted through a noncanonical pathway. We found that extracellular tyrosyl-tRNA synthetase (YRS) exhibited proinflammatory activities. In addition to acting as a monocyte/macrophage chemoattractant, YRS initiated signaling through Toll-like receptor 2 (TLR2) resulting in NF-κB activation and release of tumor necrosis factor α (TNFα) and multiple chemokines, including MIP-1α/β, CXCL8 (IL8), and CXCL1 (KC) from THP1 monocyte and peripheral blood mononuclear cell-derived macrophages. Furthermore, YRS up-regulated matrix metalloproteinase (MMP) activity in a TNFα-dependent manner in M0 macrophages. Because MMPs process a variety of intracellular proteins that also exhibit extracellular moonlighting functions, we profiled 10 MMPs for YRS cleavage and identified 55 cleavage sites by amino-terminal oriented mass spectrometry of substrates (ATOMS) positional proteomics and Edman degradation. Stable proteoforms resulted from cleavages near the start of the YRS C-terminal EMAPII domain. All of the MMPs tested cleaved at ADS386↓387LYV and VSG405↓406LVQ, generating 43- and 45-kDa fragments. The highest catalytic efficiency for YRS was demonstrated by MMP7, which is highly expressed by monocytes and macrophages, and by neutrophil-specific MMP8. MMP-cleaved YRS enhanced TLR2 signaling, increased TNFα secretion from macrophages, and amplified monocyte/macrophage chemotaxis compared with unprocessed YRS. The cleavage of YRS by MMP8, but not MMP7, was inhibited by tyrosine, a substrate of the YRS aminoacylation reaction. Overall, the proinflammatory activity of YRS is enhanced by MMP cleavage, which we suggest forms a feed-forward mechanism to promote inflammation."xsd:string |
| http://purl.uniprot.org/citations/31771979 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.ra119.010486"xsd:string |
| http://purl.uniprot.org/citations/31771979 | http://purl.uniprot.org/core/author | "Kim S."xsd:string |
| http://purl.uniprot.org/citations/31771979 | http://purl.uniprot.org/core/author | "Overall C.M."xsd:string |
| http://purl.uniprot.org/citations/31771979 | http://purl.uniprot.org/core/author | "Butler G.S."xsd:string |
| http://purl.uniprot.org/citations/31771979 | http://purl.uniprot.org/core/author | "Solis N."xsd:string |
| http://purl.uniprot.org/citations/31771979 | http://purl.uniprot.org/core/author | "Rai S.K."xsd:string |
| http://purl.uniprot.org/citations/31771979 | http://purl.uniprot.org/core/author | "Kwon N.H."xsd:string |
| http://purl.uniprot.org/citations/31771979 | http://purl.uniprot.org/core/author | "Bell P.A."xsd:string |
| http://purl.uniprot.org/citations/31771979 | http://purl.uniprot.org/core/author | "Machado Y."xsd:string |
| http://purl.uniprot.org/citations/31771979 | http://purl.uniprot.org/core/author | "Jobin P.G."xsd:string |
| http://purl.uniprot.org/citations/31771979 | http://purl.uniprot.org/core/date | "2020"xsd:gYear |
| http://purl.uniprot.org/citations/31771979 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/31771979 | http://purl.uniprot.org/core/pages | "2186-2202"xsd:string |
| http://purl.uniprot.org/citations/31771979 | http://purl.uniprot.org/core/title | "Moonlighting matrix metalloproteinase substrates: Enhancement of proinflammatory functions of extracellular tyrosyl-tRNA synthetase upon cleavage."xsd:string |
| http://purl.uniprot.org/citations/31771979 | http://purl.uniprot.org/core/volume | "295"xsd:string |
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