Aminoacyl-tRNA synthetases are a class of enzymes that charge tRNAs with their cognate amino acids. Lysyl-tRNA synthetase is a homodimer localized to the cytoplasm which belongs to the class II family of tRNA synthetases. It has been shown to be a target of autoantibodies in the human autoimmune diseases, polymyositis or dermatomyositis[3]
Besides its role in translation, Lysyl-tRNA synthetase is involved in a signaling pathway leading to gene activation.[4] Following physiological stimulation of a variety of cells, Lysyl-tRNA synthetase binds to the transcription factors MITF[5] and USF2[6] and can then influence their transcriptional activities. Such physiological stimulation includes immunological activation of mast cells, so this pathway maybe relevant to the allergic response.
KARS (gene) has been shown to interact with Multisynthetase complex auxiliary component p38.[7][8] Physiological trigger such as immunological activation results in the phosphorylation of LysRS is on serine residues. It separates from the multisynthetase complex and initiates Ap4A production.[4]
↑Nichols RC, Blinder J, Pai SI, Ge Q, Targoff IN, Plotz PH, Liu P (Aug 1996). "Assignment of two human autoantigen genes-isoleucyl-tRNA synthetase locates to 9q21 and lysyl-tRNA synthetase locates to 16q23-q24". Genomics. 36 (1): 210–3. doi:10.1006/geno.1996.0449. PMID8812440.
↑Shiba K, Stello T, Motegi H, Noda T, Musier-Forsyth K, Schimmel P (Sep 1997). "Human lysyl-tRNA synthetase accepts nucleotide 73 variants and rescues Escherichia coli double-defective mutant". The Journal of Biological Chemistry. 272 (36): 22809–16. doi:10.1074/jbc.272.36.22809. PMID9278442.
↑ 4.04.1Yannay-Cohen N, Carmi-Levy I, Kay G, Yang CM, Han JM, Kemeny DM, Kim S, Nechushtan H, Razin E (Jun 2009). "LysRS serves as a key signaling molecule in the immune response by regulating gene expression". Molecular Cell. 34 (5): 603–11. doi:10.1016/j.molcel.2009.05.019. PMID19524539.
↑Lee YN, Nechushtan H, Figov N, Razin E (Feb 2004). "The function of lysyl-tRNA synthetase and Ap4A as signaling regulators of MITF activity in FcepsilonRI-activated mast cells". Immunity. 20 (2): 145–51. doi:10.1016/S1074-7613(04)00020-2. PMID14975237.
↑Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (Oct 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. doi:10.1038/nature04209. PMID16189514.
↑Quevillon S, Robinson JC, Berthonneau E, Siatecka M, Mirande M (Jan 1999). "Macromolecular assemblage of aminoacyl-tRNA synthetases: identification of protein-protein interactions and characterization of a core protein". Journal of Molecular Biology. 285 (1): 183–95. doi:10.1006/jmbi.1998.2316. PMID9878398.
Yannay-Cohen N, Razin E (Oct 2006). "Translation and transcription: the dual functionality of LysRS in mast cells". Molecules and Cells. 22 (2): 127–32. PMID17085962.
Kleiman L, Halwani R, Javanbakht H (Apr 2004). "The selective packaging and annealing of primer tRNALys3 in HIV-1". Current HIV Research. 2 (2): 163–75. doi:10.2174/1570162043484988. PMID15078180.
Kino T, Pavlakis GN (Apr 2004). "Partner molecules of accessory protein Vpr of the human immunodeficiency virus type 1". DNA and Cell Biology. 23 (4): 193–205. doi:10.1089/104454904773819789. PMID15142377.
Kleiman L, Cen S (Sep 2004). "The tRNALys packaging complex in HIV-1". The International Journal of Biochemistry & Cell Biology. 36 (9): 1776–86. doi:10.1016/j.biocel.2004.02.022. PMID15183344.
Norcum MT (Aug 1991). "Structural analysis of the high molecular mass aminoacyl-tRNA synthetase complex. Effects of neutral salts and detergents". The Journal of Biological Chemistry. 266 (23): 15398–405. PMID1651330.
Nomura N, Nagase T, Miyajima N, Sazuka T, Tanaka A, Sato S, Seki N, Kawarabayasi Y, Ishikawa K, Tabata S (1995). "Prediction of the coding sequences of unidentified human genes. II. The coding sequences of 40 new genes (KIAA0041-KIAA0080) deduced by analysis of cDNA clones from human cell line KG-1". DNA Research. 1 (5): 223–9. doi:10.1093/dnares/1.5.223. PMID7584044.
Quevillon S, Robinson JC, Berthonneau E, Siatecka M, Mirande M (Jan 1999). "Macromolecular assemblage of aminoacyl-tRNA synthetases: identification of protein-protein interactions and characterization of a core protein". Journal of Molecular Biology. 285 (1): 183–95. doi:10.1006/jmbi.1998.2316. PMID9878398.
Tolkunova E, Park H, Xia J, King MP, Davidson E (Nov 2000). "The human lysyl-tRNA synthetase gene encodes both the cytoplasmic and mitochondrial enzymes by means of an unusual alternative splicing of the primary transcript". The Journal of Biological Chemistry. 275 (45): 35063–9. doi:10.1074/jbc.M006265200. PMID10952987.
Sang Lee J, Gyu Park S, Park H, Seol W, Lee S, Kim S (Feb 2002). "Interaction network of human aminoacyl-tRNA synthetases and subunits of elongation factor 1 complex". Biochemical and Biophysical Research Communications. 291 (1): 158–64. doi:10.1006/bbrc.2002.6398. PMID11829477.
Ahn HC, Kim S, Lee BJ (May 2003). "Solution structure and p43 binding of the p38 leucine zipper motif: coiled-coil interactions mediate the association between p38 and p43". FEBS Letters. 542 (1–3): 119–24. doi:10.1016/S0014-5793(03)00362-4. PMID12729910.
Javanbakht H, Halwani R, Cen S, Saadatmand J, Musier-Forsyth K, Gottlinger H, Kleiman L (Jul 2003). "The interaction between HIV-1 Gag and human lysyl-tRNA synthetase during viral assembly". The Journal of Biological Chemistry. 278 (30): 27644–51. doi:10.1074/jbc.M301840200. PMID12756246.
Kim MJ, Park BJ, Kang YS, Kim HJ, Park JH, Kang JW, Lee SW, Han JM, Lee HW, Kim S (Jul 2003). "Downregulation of FUSE-binding protein and c-myc by tRNA synthetase cofactor p38 is required for lung cell differentiation". Nature Genetics. 34 (3): 330–6. doi:10.1038/ng1182. PMID12819782.
Di Y, Li J, Zhang Y, He X, Lu H, Xu D, Ling J, Huo K, Wan D, Li YY, Gu J (Jun 2003). "HCC-associated protein HCAP1, a variant of GEMIN4, interacts with zinc-finger proteins". Journal of Biochemistry. 133 (6): 713–8. doi:10.1093/jb/mvg091. PMID12869526.
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