STRIPAK integrates upstream signals to initiate the Hippo kinase cascade
NATURE CELL BIOLOGY(2019)
摘要
The Hippo pathway plays a critical role in development, tissue homeostasis and organ size; its dysregulation contributes to human diseases. Although MST1/2 and the MAP4Ks are well known as the Hippo kinases, a major open question is how these kinases are regulated by upstream signals. Here we report that STRIPAK integrates upstream signals to control the activities of MST1/2 and the MAP4Ks, thus initiating Hippo signalling. STRIPAK also serves as a master regulator for the STE20 family kinases. Following serum or lysophosphatidic acid stimulation, active RhoA binds and dissociates rhophilin and NF2/Kibra from STRIPAK, thereby inducing the association and dephosphorylation of MST1/2 and MAP4Ks by the STRIPAK phosphatase catalytic subunit PP2AC. Rhophilin suppresses cancer cell growth by activating the Hippo pathway. Our study reveals a RhoA–rhophilin–NF2/Kibra–STRIPAK signalling axis in Hippo regulation, thus addressing the key question of how Hippo signalling is initiated and suggesting a broad and active role for STRIPAK in cellular signalling.
更多查看译文
关键词
HIPPO signalling,Intracellular signalling peptides and proteins,Kinases,Life Sciences,general,Cell Biology,Cancer Research,Developmental Biology,Stem Cells
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要