Abstract
The Hippo pathway is a newly identified pathway and evolutionarily conserved from flies to humans mainly regulating cell proliferation. Transcriptional co-activator Yes-associated protein (YAP) functions as a major downstream effector and key node of the Hippo pathway. Phosphorylation of YAP is critical to regulate YAP activity and its corresponding functions. β-adrenergic receptor (β-AR), a typical G protein coupled receptor (GPCR), mediates proliferation in various cell types and regulates multiple physical and pathological processes. However, the role of β-AR in regulating YAP remains elusive. Here, we report that β-AR can obviously stimulate YAP tyrosine phosphorylation. The mechanism is that β-AR stimulation results in tyrosine kinase Src activation and Src phosphorylates YAP tyrosine at Y357. Further studies demonstrate that inhibition of Src kinase activity can obviously alleviate β-AR induced YAP tyrosine phosphorylation and cell proliferation. We conclude that β-AR can induce YAP tyrosine phosphorylation and also establish the Src/YAP pathway as a critical signaling branch downstream of GPCR.
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Acknowledgements
The authors acknowledge funding support from the National Natural Science Foundation of China (91939301, 81820108031, 91539123, 81471893) and Beijing Municipal Natural Science Foundation (7172235, 7191013). The authors also thank Professor Qiaobing Huang (Department of Pathophysiology, Southern Medical University, Guangzhou, China) for providing pcDNA3.1-flag-Src plasmid, and thank Professor Hui Li (Institute of Physics, Chinese Academy of Sciences, Beijing, China) for supporting live-cell total internal reflection fluorescence microscopy imaging.
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Compliance and ethics The author(s) declare that they have no conflict of interest. For studies involving animals, the authors state that they conformed with the Helsinki Declaration of 1975 (as revised in 2008) concerning Animal Rights, and that they followed out the policy concerning Informed Consent as shown on Springer.com.
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Wang, W., Li, W., Liu, K. et al. Src mediates β-adrenergic receptor induced YAP tyrosine phosphorylation. Sci. China Life Sci. 63, 697–705 (2020). https://doi.org/10.1007/s11427-020-1652-9
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DOI: https://doi.org/10.1007/s11427-020-1652-9