RRC ID 54539
著者 Tran THY, Yang DW, Kim M, Lee DH, Gai M, Di Cunto F, Choi KW, Lim DS.
タイトル Citron kinase interacts with LATS2 and inhibits its activity by occluding its hydrophobic phosphorylation motif.
ジャーナル J Mol Cell Biol
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.
巻・号 11(11)
ページ 1006-1017
公開日 2019-12-23
DOI 10.1093/jmcb/mjz013
PII 5379217
PMID 30865227
PMC PMC6927243
MeSH Amino Acid Motifs Animals Drosophila Proteins / metabolism Drosophila melanogaster / metabolism Epistasis, Genetic Genotype Humans Hydrophobic and Hydrophilic Interactions Intracellular Signaling Peptides and Proteins / chemistry* Intracellular Signaling Peptides and Proteins / genetics Intracellular Signaling Peptides and Proteins / metabolism* Models, Biological Nuclear Proteins / metabolism Phenotype Phosphorylation Protein Binding Protein Interaction Domains and Motifs* Protein Serine-Threonine Kinases / antagonists & inhibitors* Protein Serine-Threonine Kinases / chemistry Protein Serine-Threonine Kinases / genetics Protein Serine-Threonine Kinases / metabolism* Trans-Activators / metabolism YAP-Signaling Proteins
IF 4.671
引用数 0
リソース情報
ショウジョウバエ 10522R-1 10522R-2 DGRC#201488