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Chemical inhibition of prometastatic lysyl-tRNA synthetase-laminin receptor interaction.

Title: Chemical inhibition of prometastatic lysyl-tRNA synthetase-laminin receptor interaction.
Name(s): Kim, Dae Gyu, author
Lee, Jin Young, author
Kwon, Nam Hoon, author
Fang, Pengfei, author
Zhang, Qian, author
Wang, Jing, author
Young, Nicolas L, author
Guo, Min, author
Cho, Hye Young, author
Mushtaq, Ameeq Ul, author
Jeon, Young Ho, author
Choi, Jin Woo, author
Han, Jung Min, author
Kang, Ho Woong, author
Joo, Jae Eun, author
Hur, Youn, author
Kang, Wonyoung, author
Yang, Heekyoung, author
Nam, Do-Hyun, author
Lee, Mi-Sook, author
Lee, Jung Weon, author
Kim, Eun-Sook, author
Moon, Aree, author
Kim, Kibom, author
Kim, Doyeun, author
Kang, Eun Joo, author
Moon, Youngji, author
Rhee, Kyung Hee, author
Han, Byung Woo, author
Yang, Jee Sun, author
Han, Gyoonhee, author
Yang, Won Suk, author
Lee, Cheolju, author
Wang, Ming-Wei, author
Kim, Sunghoon, author
Type of Resource: text
Genre: Journal Article
Date Issued: 2014-01-01
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: Lysyl-tRNA synthetase (KRS), a protein synthesis enzyme in the cytosol, relocates to the plasma membrane after a laminin signal and stabilizes a 67-kDa laminin receptor (67LR) that is implicated in cancer metastasis; however, its potential as an antimetastatic therapeutic target has not been explored. We found that the small compound BC-K-YH16899, which binds KRS, impinged on the interaction of KRS with 67LR and suppressed metastasis in three different mouse models. The compound inhibited the KRS-67LR interaction in two ways. First, it directly blocked the association between KRS and 67LR. Second, it suppressed the dynamic movement of the N-terminal extension of KRS and reduced membrane localization of KRS. However, it did not affect the catalytic activity of KRS. Our results suggest that specific modulation of a cancer-related KRS-67LR interaction may offer a way to control metastasis while avoiding the toxicities associated with inhibition of the normal functions of KRS.
Identifier: FSU_pmch_24212136 (IID), 10.1038/nchembio.1381 (DOI), PMC4021855 (PMCID), 24212136 (RID), 24212136 (EID), nchembio.1381 (PII)
Grant Number: R01 GM100136, R01 GM106134, GM100136
Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at
Subject(s): Cell Membrane/metabolism
Lysine-tRNA Ligase/antagonists & inhibitors
Lysine-tRNA Ligase/metabolism
Neoplasm Metastasis
Protein Transport
Receptors, Laminin/antagonists & inhibitors
Receptors, Laminin/metabolism
Persistent Link to This Record:
Owner Institution: FSU
Is Part Of: Nature chemical biology.
Issue: iss. 1, vol. 10

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Kim, D. G., Lee, J. Y., Kwon, N. H., Fang, P., Zhang, Q., Wang, J., … Kim, S. (2014). Chemical inhibition of prometastatic lysyl-tRNA synthetase-laminin receptor interaction. Nature Chemical Biology. Retrieved from