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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Depletion of Janus kinase-2 promotes neuronal differentiation of mouse embryonic stem cells

  • Oh, Mihee (Biodefense Research Center) ;
  • Kim, Sun Young (Biodefense Research Center) ;
  • Byun, Jeong-Su (Biodefense Research Center) ;
  • Lee, Seonha (Biodefense Research Center) ;
  • Kim, Won-Kon (Metabolic Regulation Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Oh, Kyoung-Jin (Metabolic Regulation Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Lee, Eun-Woo (Metabolic Regulation Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Bae, Kwang-Hee (Metabolic Regulation Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Lee, Sang Chul (Metabolic Regulation Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Han, Baek-Soo (Biodefense Research Center)
  • Received : 2021.10.30
  • Accepted : 2021.11.15
  • Published : 2021.12.31
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Abstract

Janus kinase 2 (JAK2), a non-receptor tyrosine kinase, is a critical component of cytokine and growth factor signaling pathways regulating hematopoietic cell proliferation. JAK2 mutations are associated with multiple myeloproliferative neoplasms. Although physiological and pathological functions of JAK2 in hematopoietic tissues are well-known, such functions of JAK2 in the nervous system are not well studied yet. The present study demonstrated that JAK2 could negatively regulate neuronal differentiation of mouse embryonic stem cells (ESCs). Depletion of JAK2 stimulated neuronal differentiation of mouse ESCs and activated glycogen synthase kinase 3β, Fyn, and cyclin-dependent kinase 5. Knockdown of JAK2 resulted in accumulation of GTP-bound Rac1, a Rho GTPase implicated in the regulation of cytoskeletal dynamics. These findings suggest that JAK2 might negatively regulate neuronal differentiation by suppressing the GSK-3β/Fyn/CDK5 signaling pathway responsible for morphological maturation.

Keywords

Acknowledgement

This work was supported by grants from the Defense Acquisition Program Administration (ADD-911255201).

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