title: Roles of mammalian sterile 20-like kinase 2-dependent phosphorylations of Mps one binder 1B in the activation of nuclear Dbf2-related kinases.
abstract: Mammalian nuclear Dbf2-related (NDR) kinases (LATS1, LATS2, NDR1 and NDR2) play a role in cell proliferation, apoptosis and morphological changes. Mammalian sterile 20-like (MST) kinases and Mps one binder (MOB) proteins are important in the activation of NDR kinases. MOB1 is phosphorylated by MST1 and MST2 and this phosphorylation enhances the ability of MOB1 to activate NDR kinases. The phosphorylated MOB1 can be more effective as a scaffold protein to facilitate the MST-dependent phosphorylation of NDR kinases and/or as a direct activator of NDR kinases. We previously reported that Thr74 of MOB1B is phosphorylated by MST2. Thr12 and Thr35 have also been identified as phosphorylation sites. In this study, we quantified the phosphorylation of Thr74 using the phosphorylated Thr74-specific antibody. Thr74 is indeed phosphorylated by MST2, but the efficiency is low, suggesting that MOB1B can activate NDR kinases without the phosphorylation of Thr74. We also showed that the phosphorylated MOB1B activates NDR1 T444D and LATS2 T1041D, in which threonine residues phosphorylated by MST kinases are replaced with phosphorylation-mimicking aspartic acid, more efficiently than the unphosphorylated MOB1B does. This finding supports that the phosphorylation of MOB1B enhances its ability as a direct activator of NDR kinases.
authors.affiliation: Department of Medical Biochemistry, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Bao
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Sumita
authors.forename: Takumi
authors.initials: T
authors.lastname: Kudo
authors.forename: Kanchanamala
authors.initials: K
authors.lastname: Withanage
authors.forename: Kentaro
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Mitsunobu
authors.initials: M
authors.lastname: Ikeda
authors.forename: Kikuo
authors.initials: K
authors.lastname: Ohno
authors.forename: Yunjie
authors.initials: Y
authors.lastname: Wang
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hata
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D004789:Enzyme Activation; D006801:Humans; D047468:Immunoprecipitation; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000090742:Serine-Threonine Kinase 3; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D000099317:Hippo Kinases
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D000090742:Serine-Threonine Kinase 3; D025521:Tumor Suppressor Proteins; C496256:MOB1A protein, human; C406449:LATS2 protein, human; C097835:STK3 protein, human; D000099317:Hippo Kinases; C491614:STK38 protein, human