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The origin of GSKIP, a multifaceted regulatory factor in the mammalian Wnt pathway.
Chou, Chia-Hua; Yang, Ming-Chang; Hsiao, Bo-Xiu; Wang, Yin-Hsuan; Liu, Hsin-Fu; Chiou, Shean-Jaw; Chuang, Yu-Chung; Yang, Chia-Ning; Lieu, Ann-Shung; Loh, Joon-Khim; Howng, Shen-Long; Chou, An-Kuo; Tseng, Chao-Neng; Cheng, Jiin-Tsuey; Hong, Yi-Ren.
Afiliación
  • Chou CH; Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Biochemistry, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
  • Yang MC; Laboratories of Medical Research, Center for Education and Faculty Development, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan.
  • Hsiao BX; Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
  • Wang YH; Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.
  • Liu HF; Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan.
  • Chiou SJ; Department of Biochemistry, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
  • Chuang YC; Department of Life Sciences, National University of Kaohsiung, Kaohsiung, Taiwan.
  • Yang CN; Department of Life Sciences, National University of Kaohsiung, Kaohsiung, Taiwan.
  • Lieu AS; Department of Neurosurgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
  • Loh JK; Department of Neurosurgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Surgery, Kaohsiung Municipal Da-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
  • Howng SL; Department of Neurosurgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
  • Chou AK; Department of Anesthesiology, China Medical University Hospital, Taichung, Taiwan.
  • Tseng CN; Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Biochemistry, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
  • Cheng JT; Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.
  • Hong YR; Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Biochemistry, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan; Department of
Biochim Biophys Acta Mol Cell Res ; 1865(8): 1046-1059, 2018 08.
Article en En | MEDLINE | ID: mdl-29694914
GSK3ß interacting protein (GSKIP) is a naturally occurring negative regulator of GSK3ß and retains both the Protein Kinase A Regulatory subunit binding (PKA-RII) domain and GSK3ß interacting domain. Of these two domains, we found that PKA-RII is required for forming a working complex comprising PKA/GSKIP/GSK3ß/Drp1 to influence phosphorylation of Drp1 Ser637. In this study, bioinformatics and experimental explorations re-analyzing GSKIP's biofunctions suggest that the evolutionarily conserved Domain of Unknown Function (DUF727) is an ancestral prototype of GSKIP in prokaryotes, and acquired the C-terminal GSK3ß binding site (tail) in invertebrates except for Saccharomyces spp., after which the N-terminal PKA-RII binding region (head) evolved in vertebrates. These two regions mutually influence each other and modulate GSKIP binding to GSK3ß in yeast two-hybrid assays and co-immunoprecipitation. Molecular modeling showed that mammalian GSKIP could form a dimer through the L130 residue (GSK3ß binding site) rather than V41/L45 residues. In contrast, V41/L45P mutant facilitated a gain-of-function effect on GSKIP dimerization, further influencing binding behavior to GSK3ß compared to GSKIP wild-type (wt). The V41/L45 residues are not only responsible for PKA RII binding that controls GSK3ß activity, but also affect dimerization of GSKIP monomer, with net results of gain-of-function in GSKIP-GSK3ß interaction. In addition to its reported role in modulating Drp1, Ser637 phosphorylation caused mitochondrial elongation; we postulated that GSKIP might be involved in the Wnt signaling pathway as a scavenger to recruit GSK3ß away from the ß-catenin destruction complex and as a competitor to compete for GSK3ß binding, resulting in accumulation of S675 phosphorylated ß-catenin.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Represoras / Vía de Señalización Wnt Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Biochim Biophys Acta Mol Cell Res Año: 2018 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Represoras / Vía de Señalización Wnt Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Biochim Biophys Acta Mol Cell Res Año: 2018 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Países Bajos