Keratins regulate Hsp70-mediated nuclear localization of p38 mitogen-activated protein kinase

So Young Lee, Sujin Kim, Younglan Lim, Han Na Yoon, Nam On Ku

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7 Citations (Scopus)


Intermediate filament protein keratin 8 (K8) binds to heat shock protein 70 (Hsp70) and p38 MAPK, and is phosphorylated at Ser74 by p38α(MAPK14, hereafter p38). However, a p38 binding site on K8 and the molecular mechanism of K8-p38 interaction related to Hsp70 are unknown. Here, we idenstify a p38 docking site on K8 (Arg148/149 and Leu159/161) that is highly conserved in other intermediate filaments. A docking-deficient K8 mutation caused increased p38-Hsp70 interaction and enhanced p38 nuclear localization, indicating that the p38 dissociated from mutant K8 makes a complex with Hsp70, which is known as a potential chaperone for p38 nuclear translocation. Comparison of p38 MAPK binding with keratin variants associated with liver disease showed that the K18 I150V variant dramatically reduced binding with p38, which is similar to the effect of the p38 docking-deficient mutation on K8. Because the p38 docking site on K8 (Arg148/149 and Leu159/ 161) and the K18 Ile150 residue are closely localized in the parallel K8/K18 heterodimer, the K18 I150V mutation might interfere with K8- p38 interaction. These findings show that keratins, functioning as cytoplasmic anchors for p38, modulate p38 nuclear localization and thereby might affect a number of p38-mediated signal transduction pathways.

Original languageEnglish
Article numberjcs229534
JournalJournal of cell science
Issue number18
Publication statusPublished - 2019 Sept

Bibliographical note

Funding Information:
This work was supported by the Korean Ministry of Education, Science, and Technology (grants 2016R1A2B4012808 and 2018R1D1A1A02086060 to N.-O.K.) and the Yonsei University Research Fund (2018-22-0072 to N.-O.K.).

Publisher Copyright:
© 2019. Published by The Company of Biologists Ltd.

All Science Journal Classification (ASJC) codes

  • Cell Biology


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