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http://purl.uniprot.org/citations/20231902http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/20231902http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/20231902http://www.w3.org/2000/01/rdf-schema#comment"

Background

Hippo, a Drosophila serine/threonine kinase, promotes apoptosis and restricts cell growth and proliferation. Its mammalian homolog MST2 has been shown to play similar role and be regulated by Raf-1 via a kinase-independent mechanism and by RASSF family proteins through forming complex with MST2. However, regulation of MST2 by cell survival signal remains largely unknown.

Methodology/principal findings

Using immunoblotting, in vitro kinase and in vivo labeling assays, we show that IGF1 inhibits MST2 cleavage and activation induced by DNA damage through the phosphatidylinosotol 3-kinase (PI3K)/Akt pathway. Akt phosphorylates a highly conserved threonine-117 residue of MST2 in vitro and in vivo, which leads to inhibition of MST2 cleavage, nuclear translocation, autophosphorylation-Thr180 and kinase activity. As a result, MST2 proapoptotic and growth arrest function was significantly reduced. Further, inverse correlation between pMST2-T117/pAkt and pMST2-T180 was observed in human breast tumors.

Conclusions/significance

Our findings demonstrate for the first time that extracellular cell survival signal IGF1 regulates MST2 and that Akt is a key upstream regulator of MST2."xsd:string
http://purl.uniprot.org/citations/20231902http://purl.org/dc/terms/identifier"doi:10.1371/journal.pone.0009616"xsd:string
http://purl.uniprot.org/citations/20231902http://purl.org/dc/terms/identifier"doi:10.1371/journal.pone.0009616"xsd:string
http://purl.uniprot.org/citations/20231902http://purl.uniprot.org/core/author"Kim D."xsd:string
http://purl.uniprot.org/citations/20231902http://purl.uniprot.org/core/author"Kim D."xsd:string
http://purl.uniprot.org/citations/20231902http://purl.uniprot.org/core/author"Shu S."xsd:string
http://purl.uniprot.org/citations/20231902http://purl.uniprot.org/core/author"Shu S."xsd:string
http://purl.uniprot.org/citations/20231902http://purl.uniprot.org/core/author"Kaneko S."xsd:string
http://purl.uniprot.org/citations/20231902http://purl.uniprot.org/core/author"Kaneko S."xsd:string
http://purl.uniprot.org/citations/20231902http://purl.uniprot.org/core/author"Cheng J.Q."xsd:string
http://purl.uniprot.org/citations/20231902http://purl.uniprot.org/core/author"Cheng J.Q."xsd:string
http://purl.uniprot.org/citations/20231902http://purl.uniprot.org/core/author"Coppola M.D."xsd:string
http://purl.uniprot.org/citations/20231902http://purl.uniprot.org/core/author"Coppola M.D."xsd:string
http://purl.uniprot.org/citations/20231902http://purl.uniprot.org/core/author"Yuan Z.Q."xsd:string
http://purl.uniprot.org/citations/20231902http://purl.uniprot.org/core/author"Yuan Z.Q."xsd:string
http://purl.uniprot.org/citations/20231902http://purl.uniprot.org/core/date"2010"xsd:gYear
http://purl.uniprot.org/citations/20231902http://purl.uniprot.org/core/date"2010"xsd:gYear
http://purl.uniprot.org/citations/20231902http://purl.uniprot.org/core/name"PLoS ONE"xsd:string
http://purl.uniprot.org/citations/20231902http://purl.uniprot.org/core/name"PLoS ONE"xsd:string
http://purl.uniprot.org/citations/20231902http://purl.uniprot.org/core/pages"E9616"xsd:string
http://purl.uniprot.org/citations/20231902http://purl.uniprot.org/core/pages"E9616"xsd:string
http://purl.uniprot.org/citations/20231902http://purl.uniprot.org/core/title"Regulation of proapoptotic mammalian ste20-like kinase MST2 by the IGF1-Akt pathway."xsd:string
http://purl.uniprot.org/citations/20231902http://purl.uniprot.org/core/title"Regulation of proapoptotic mammalian ste20-like kinase MST2 by the IGF1-Akt pathway."xsd:string
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