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

作　　者：Thi Hai Yen Tran Dae-Wook Yang Minchul Kim Da-Hye Lee Marta Gai Ferdinando Di Cunto Kwang-Wook Choi Dae-Sik Lim 

机构地区：[1]Department of Biological Sciences,KAIST 291 Daehak-ro,Yuseong-gu,Daejeon 34141,Republic of Korea [2]Department of Molecular Biotechnology and Health Sciences,University of Turin,10126 Turin,Italy

出　　处：《Journal of Molecular Cell Biology》2019年第11期1006-1017,共12页分子细胞生物学报（英文版）

摘　　要：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 CITs 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 Unking 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.

关 键 词：citron kinase LATS2-YAP interaction LATS2 inhibition sticky-warts Hippo pathway 

分 类 号：R73[医药卫生—肿瘤]