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 downs...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 ofβ-AR in regulating YAP remains elusive.Here,we report thatβ-AR can obviously stimulate YAP tyrosine phosphorylation.The mechanism is thatβ-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 alleviateβ-AR induced YAP tyrosine phosphorylation and cell proliferation.We conclude thatβ-AR can induce YAP tyrosine phosphorylation and also establish the Src/YAP pathway as a critical signaling branch downstream of GPCR.展开更多
基金funding support from the National Natural Science Foundation of China(91939301,81820108031,91539123,81471893)Beijing Municipal Natural Science Foundation(7172235,7191013)。
文摘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 ofβ-AR in regulating YAP remains elusive.Here,we report thatβ-AR can obviously stimulate YAP tyrosine phosphorylation.The mechanism is thatβ-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 alleviateβ-AR induced YAP tyrosine phosphorylation and cell proliferation.We conclude thatβ-AR can induce YAP tyrosine phosphorylation and also establish the Src/YAP pathway as a critical signaling branch downstream of GPCR.
