Interaction of two translational components, lysyl-tRNA synthetase and p40/37LRP, in plasma membrane promotes laminin-dependent cell migration

Dae Gyu Kim, Jin Woo Choi, Jin Young Lee, Hyerim Kim, Young Sun Oh, Jung Weon Lee, Yu Kyung Tak, Joon Myong Song, Ehud Razin, Seok Hyun Yun, Sunghoon Kim

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45 Citations (Scopus)

Abstract

Although human lysyl-tRNA synthetase (KRS), an enzyme for protein synthesis, is often highly expressed in various cancer cells, its pathophysiological implications have not been understood. Here we found that KRS induces cancer cell migration through interaction with the 67-kDa laminin receptor (67LR) that is converted from ribosomal subunit p40. On laminin signal, KRS was phosphorylated at the T52 residue by p38MAPK and dissociated from the cytosolic multitRNA synthetase complex for membrane translocation. The importance of T52 phosphorylation for membrane translocation of KRS was confirmed by site-directed mutagenesis. In the membrane, turnover of 67LR was controlled by Nedd4-mediated ubiquitination, and KRS inhibited ubiquitin-dependent degradation of 67LR, thereby enhancing laminin-induced cell migration. This work thus unveiled a unique function of KRS in the control of cell migration and its pathological implication in metastasis.

Original languageEnglish
Pages (from-to)4142-4159
Number of pages18
JournalFASEB Journal
Volume26
Issue number10
DOIs
Publication statusPublished - 2012 Oct 1

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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    Kim, D. G., Choi, J. W., Lee, J. Y., Kim, H., Oh, Y. S., Lee, J. W., Tak, Y. K., Song, J. M., Razin, E., Yun, S. H., & Kim, S. (2012). Interaction of two translational components, lysyl-tRNA synthetase and p40/37LRP, in plasma membrane promotes laminin-dependent cell migration. FASEB Journal, 26(10), 4142-4159. https://doi.org/10.1096/fj.12-207639