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Regulation of the Hippo-YAP pathway by G-protein-coupled receptor signaling

热1 聚焦生物添加于 2012-12-26 22:00 | 10230 次阅读 | 1 个评论

作者
Yu F-X, Zhao B, Panupinthu N, Jewell JL, Lian I, Wang LH, Zhao J, Yuan H, Tumaneng K, Li H, Fu X-D, Mills GB, Guan K-L
摘要
The Hippo pathway is crucial in organ size control, and its dysregulation contributes to tumorigenesis. However, upstream signals that regulate the mammalian Hippo pathway have remained elusive. Here, we report that the Hippo pathway is regulated by G-protein-coupled receptor (GPCR) signaling. Serum-borne lysophosphatidic acid (LPA) and sphingosine 1-phosphophate (S1P) act through G12/13-coupled receptors to inhibit the Hippo pathway kinases Lats1/2, thereby activating YAP and TAZ transcription coactivators, which are oncoproteins repressed by Lats1/2. YAP and TAZ are involved in LPA-induced gene expression, cell migration, and proliferation. In contrast, stimulation of Gs-coupled receptors by glucagon or epinephrine activates Lats1/2 kinase activity, thereby inhibiting YAP function. Thus, GPCR signaling can either activate or inhibit the Hippo-YAP pathway depending on the coupled G protein. Our study identifies extracellular diffusible signals that modulate the Hippo pathway and also establishes the Hippo-YAP pathway as a critical signaling branch downstream of GPCR.
详细资料
- 关键词: Animals; Cell Line; Cell Movement; Cell Proliferation; Humans; Lysophospholipids/metabolism; Neoplasms/metabolism; Nuclear Proteins/metabolism; Organ Size; Phosphorylation; Protein-Serine-Threonine Kinases/metabolism; Receptors, G-Protein-Coupled/*metabolism; Serum/chemistry; *Signal Transduction; Sphingosine/analogs & derivatives/metabolism; Transcription Factors/metabolism
- 文献种类: Journal Article
- 期刊名称: Cell
- 期刊缩写: Cell
- 期卷页: 2012年第150卷第4期 780-791页
- 地址: Department of Pharmacology and Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA
- ISBN: 0092-8674
学科领域生物医药 » 生物学
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附件
Regulation of the Hippo-YAP pathway by G-protein-coupled receptor signaling