Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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The PPLA Motif of Glycogen Synthase Kinase 3β Is Required for Interaction with Fe65

  • Lee, Eun Jeoung (School of Science Education, Chungbuk National University) ;
  • Hyun, Sunghee (Department of Pre-medicine, Eulji University School of Medicine) ;
  • Chun, Jaesun (Department of Biology Education, Korea National University of Education) ;
  • Shin, Sung Hwa (School of Science Education, Chungbuk National University) ;
  • Lee, Kyung Eun (School of Science Education, Chungbuk National University) ;
  • Yeon, Kwang Hum (Department of Biology Education, Korea National University of Education) ;
  • Park, Tae Yoon (Graduate School of Education, Yonsei University) ;
  • Kang, Sang Sun (School of Science Education, Chungbuk National University)
  • Received : 2008.01.11
  • Accepted : 2008.02.05
  • Published : 2008.07.31
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Abstract

Glycogen synthase kinase $3{\beta}$ (GSK $3{\beta}$) is a serine/threonine kinase that phosphorylates substrates such as ${\beta}$-catenin and is involved in a variety of biological processes, including embryonic development, metabolism, tumorigenesis, and cell death. Here, we present evidence that human GSK $3{\beta}$ is associated with Fe65, which has the characteristics of an adaptor protein, possessing a WW domain, and two phosphotyrosine interaction domains, PID1 and PID2. The GSK $3{\beta}$ catalytic domain also contains a putative WW domain binding motif ($^{371}PPLA^{374}$), and we observed, using a pull down approach and co-immunoprecipitation, that it interacts physically with Fe65 via this motif. In addition, we detected co-localization of GSK $3{\beta}$ and Fe65 by confocal microscopy, and this co-localization was disrupted by mutation of the putative WW domain binding motif of GSK $3{\beta}$. Finally, in transient transfection assays interaction of GSK $3{\beta}$ (wt) with Fe65 induced substantial cell apoptosis, whereas interaction with the GSK $3{\beta}$ AALA mutant ($^{371}AALA^{374}$) did not, and we noted that phosphorylation of the Tyr 216 residue of the GSK $3{\beta}$ AALA mutant was significantly reduced compared to that of GSK $3{\beta}$ wild type. Thus, our observations indicate that GSK $3{\beta}$ binds to Fe65 through its $^{371}PPLA^{374}$ motif and that this interaction regulates apoptosis and phosphorylation of Tyr 216 of GSK $3{\beta}$.

Keywords

Acknowledgement

Supported by : Korea Science and Engineering Foundation

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