Mst2 and Lats kinases regulate apoptotic function of Yes kinase-associated protein (YAP).
作者： Tsutomu Oka , Virginia Mazack , Marius Sudol
关键词: Cytoplasm 、 Cell biology 、 Hippo signaling pathway 、 Phosphorylation 、 Kinase 、 HEK 293 cells 、 Transcription factor 、 Tumor Protein p73 、 Signal transducing adaptor protein 、 Biology
摘要: The Hippo pathway in Drosophila controls the size and shape of organs. In fly, activation this conveys growth-inhibitory signals promotes apoptosis epithelial cells. We "reconstituted" a human cell line showed that, contrast to flies, results anti-apoptotic signals. have shown that embryonic kidney (HEK) 293 cells, complex formation between transcriptional co-activators YAPs (Yes kinase-associated proteins) Lats kinases requires intact WW domains YAPs, as well Pro-Pro-AA-Tyr (where AA is any amino acid) motifs kinases. These cooperate with upstream Mst2 kinase phosphorylate at Ser-127. Overexpression YAP2 HEK293 cells promoted apoptosis, whereas Mst2/Lats1-induced phosphorylation YAP partially rescued from apoptotic death. Apoptotic signaling was mediated via stabilization p73, which formed YAP2. All components we studied were localized cytoplasm, exception YAP, also nucleus. localization nucleus negatively controlled by Lats1 kinase. Our "readout" represents useful experimental system for identification putative receptor, membrane protein, or extracellular factor initiates an entire cascade ultimately
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