The inhibitory effect of large tumor suppressor kinase(LATS1/2)on the activity of the oncoprotein yes-associated protein(YAP)is crucial to maintain tissue homeostasis.Proteomic studies have identified several new regu...The inhibitory effect of large tumor suppressor kinase(LATS1/2)on the activity of the oncoprotein yes-associated protein(YAP)is crucial to maintain tissue homeostasis.Proteomic studies have identified several new regulators of this process.Recently,citron kinase(CIT)was listed as a potential binding candidate of Hippo-related components,suggesting a new connection between CIT and the Hippo pathway.Aside from CITs role in cytokinesis,the molecular crosstalk between CIT and the Hippo pathway is largely unknown.Here,we demonstrate a role for CIT as a scaffold protein Unking LATS2 and YAP.More importantly,CIT interacts with LATS2 to directly suppress LATS2 phosphorylation at the hydrophobic motif—targeted by MST1,leading to LATS2 inactivation and YAP activation.By studying their genetic interactions,we found that Sticky,the CIT homolog in Drosophila melanogaster,functions with Warts to control Drosophila eye development.Together,our study confirms citron kinase as a novel regulator of the Hippo pathway.展开更多
文摘The inhibitory effect of large tumor suppressor kinase(LATS1/2)on the activity of the oncoprotein yes-associated protein(YAP)is crucial to maintain tissue homeostasis.Proteomic studies have identified several new regulators of this process.Recently,citron kinase(CIT)was listed as a potential binding candidate of Hippo-related components,suggesting a new connection between CIT and the Hippo pathway.Aside from CITs role in cytokinesis,the molecular crosstalk between CIT and the Hippo pathway is largely unknown.Here,we demonstrate a role for CIT as a scaffold protein Unking LATS2 and YAP.More importantly,CIT interacts with LATS2 to directly suppress LATS2 phosphorylation at the hydrophobic motif—targeted by MST1,leading to LATS2 inactivation and YAP activation.By studying their genetic interactions,we found that Sticky,the CIT homolog in Drosophila melanogaster,functions with Warts to control Drosophila eye development.Together,our study confirms citron kinase as a novel regulator of the Hippo pathway.
