Citron kinase interacts with LATS2 and inhibits its activity by occluding its hydrophobic phosphorylation motif

Thi Hai Yen Tran, Dae Wook Yang, Minchul Kim, Da Hye Lee, Marta Gai, Ferdinando DI Cunto, Kwang Wook Choi, Dae Sik Lim

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5 Citations (Scopus)

Abstract

The inhibitory effect of large tumor suppressor kinase (LATS1/2) on the activity of the oncoprotein yes-associated protein (YAP) is crucial to maintain tissue homeostasis. Proteomic studies have identified several new regulators of this process. Recently, citron kinase (CIT) was listed as a potential binding candidate of Hippo-related components, suggesting a new connection between CIT and the Hippo pathway. Aside from CIT's role in cytokinesis, the molecular crosstalk between CIT and the Hippo pathway is largely unknown. Here, we demonstrate a role for CIT as a scaffold protein linking LATS2 and YAP. More importantly, CIT interacts with LATS2 to directly suppress LATS2 phosphorylation at the hydrophobic motif - targeted by MST1, leading to LATS2 inactivation and YAP activation. By studying their genetic interactions, we found that Sticky, the CIT homolog in Drosophila melanogaster, functions with Warts to control Drosophila eye development. Together, our study confirms citron kinase as a novel regulator of the Hippo pathway.

Original languageEnglish
Pages (from-to)1006-1017
Number of pages12
JournalJournal of Molecular Cell Biology
Volume11
Issue number11
DOIs
Publication statusPublished - Nov 2019
Externally publishedYes

Keywords

  • citron kinase
  • Hippo pathway
  • LATS2 inhibition
  • LATS2-YAP interaction
  • sticky-warts

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