Dimerization and Cytoplasmic Localization Regulate Hippo Kinase Signaling Activity in Organ Size Control

	Dimerization and Cytoplasmic Localization Regulate Hippo Kinase Signaling Activity in Organ Size Control
	Jin, YY; Dong, L; Lu, Y; Wu, WQ; Hao, Q; Zhou, ZC; Jiang, J; Zhao, Y; Zhang, L
刊名	JOURNAL OF BIOLOGICAL CHEMISTRY
	2012
卷号	287 期号:8 页码:5784-5796
通讯作者	Zhao, Y (reprint author), Chinese Acad Sci, Hundred Talents Program, Beijing 100864, Peoples R China.,yunzhao@sibs.ac.cn ; rayzhang@sibs.ac.cn
英文摘要	The Hippo (Hpo) signaling pathway controls organ size by regulating the balance between cell proliferation and apoptosis. Although the Hpo function is conserved, little is known about the mechanism of how its kinase activity is regulated. Based on structural information, we performed mutation-function analysis and provided in vitro and in vivo evidence that Hpo activation requires proper dimerization of its N-terminal kinase domain as well as the C-terminal SARAH domain. Hpo carrying point mutation M242E can still dimerize, yet the dimers formed between intermolecular kinase domains were altered in conformation. As a result, autophosphorylation of Hpo at Thr-195 was blocked, and its kinase activity was abolished. In contrast, Hpo carrying I634D, a single mutation introduced in the Hpo C-terminal SARAH domain, disrupted the dimerization of the SARAH domain, leading to reduced Hippo activity. We also find that the Hpo C-terminal half contains two nuclear export signals that promote cytoplasmic localization and activity of Hpo. Taken together, our results suggest that dimerization and nucleocytoplasmic translocation of Hpo are crucial for its biological function and indicate that a proper dimer conformation of the kinase domain is essential for Hpo autophosphorylation and kinase activity.
学科主题	Biochemistry & Molecular Biology
类目[WOS]	Biochemistry & Molecular Biology
关键词[WOS]	TUMOR-SUPPRESSOR PATHWAY ; CELL-CYCLE EXIT ; PROMOTES APOPTOSIS ; DROSOPHILA HOMOLOG ; TEAD/TEF FAMILY ; PROTEIN-KINASE ; GROWTH-CONTROL ; MST1 KINASE ; PROLIFERATION ; ACTIVATION
收录类别	SCI
语种	英语
WOS记录号	WOS:000300638000054
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/635]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Jin, YY,Dong, L,Lu, Y,et al. Dimerization and Cytoplasmic Localization Regulate Hippo Kinase Signaling Activity in Organ Size Control[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2012,287(8):5784-5796.
APA	Jin, YY.,Dong, L.,Lu, Y.,Wu, WQ.,Hao, Q.,...&Zhang, L.(2012).Dimerization and Cytoplasmic Localization Regulate Hippo Kinase Signaling Activity in Organ Size Control.JOURNAL OF BIOLOGICAL CHEMISTRY,287(8),5784-5796.
MLA	Jin, YY,et al."Dimerization and Cytoplasmic Localization Regulate Hippo Kinase Signaling Activity in Organ Size Control".JOURNAL OF BIOLOGICAL CHEMISTRY 287.8(2012):5784-5796.