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http://dx.doi.org/10.5483/BMBRep.2021.54.12.154

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)
Publication Information
BMB Reports / v.54, no.12, 2021 , pp. 626-631 More about this Journal
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
Cyclin-dependent kinase 5 (CDK5); Embryonic stem cell; Glycogen synthase kinase $3{\beta}$ (GSK3 ${\beta}$); Janus kinase-2 (JAK2); Neurogenesis; Neuronal differentiation;
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1 Spittaels K, Van den Haute C, Van Dorpe J et al (2000) Glycogen synthase kinase-3beta phosphorylates protein tau and rescues the axonopathy in the central nervous system of human four-repeat tau transgenic mice. J Biol Chem 275, 41340-41349   DOI
2 Yoshimura T, Kawano Y, Arimura N, Kawabata S, Kikuchi A and Kaibuchi K (2005) GSK-3beta regulates phosphorylation of CRMP-2 and neuronal polarity. Cell 120, 137-149   DOI
3 Cole AR (2012) GSK3 as a sensor determining cell fate in the brain. Front Mol Neurosci 5, 4   DOI
4 Chiba T, Yamada M and Aiso S (2009) Targeting the JAK2/STAT3 axis in Alzheimer's disease. Expert Opin Ther Targets 13, 1155-1167   DOI
5 Kurosu T, Nagao T, Wu N, Oshikawa G and Miura O (2013) Inhibition of the PI3K/Akt/GSK3 pathway downstream of BCR/ABL, Jak2-V617F, or FLT3-ITD downregulates DNA damage-induced Chk1 activation as well as G2/M arrest and prominently enhances induction of apoptosis. PLoS One 8, e79478   DOI
6 Nikolic M, Dudek H, Kwon YT, Ramos YF and Tsai LH (1996) The cdk5/p35 kinase is essential for neurite outgrowth during neuronal differentiation. Genes Dev 10, 816-825   DOI
7 Behrmann I, Smyczek T, Heinrich PC et al (2004) Janus kinase (Jak) subcellular localization revisited: the exclusive membrane localization of endogenous Janus kinase 1 by cytokine receptor interaction uncovers the Jak.receptor complex to be equivalent to a receptor tyrosine kinase. J Biol Chem 279, 35486-35493   DOI
8 Lee H, Jeong AJ and Ye SK (2019) Highlighted STAT3 as a potential drug target for cancer therapy. BMB Rep 52, 415-423   DOI
9 Tups A (2009) Physiological models of leptin resistance. J Neuroendocrinol 21, 961-971   DOI
10 Jain AK and Jaiswal AK (2007) GSK-3beta acts upstream of Fyn kinase in regulation of nuclear export and degradation of NF-E2 related factor 2. J Biol Chem 282, 16502-16510   DOI
11 Bibb JA, Chen J, Taylor JR et al (2001) Effects of chronic exposure to cocaine are regulated by the neuronal protein Cdk5. Nature 410, 376-380   DOI
12 Raftopoulou M and Hall A (2004) Cell migration: Rho GTPases lead the way. Dev Biol 265, 23-32   DOI
13 De-Fraja C, Conti L, Magrassi L, Govoni S and Cattaneo E (1998) Members of the JAK/STAT proteins are expressed and regulated during development in the mammalian forebrain. J Neurosci Res 54, 320-330   DOI
14 Doble BW, Patel S, Wood GA, Kockeritz LK and Woodgett JR (2007) Functional redundancy of GSK-3alpha and GSK3beta in Wnt/beta-catenin signaling shown by using an allelic series of embryonic stem cell lines. Dev Cell 12, 957-971   DOI
15 Nikolic M, Chou MM, Lu W, Mayer BJ and Tsai LH (1998) The p35/Cdk5 kinase is a neuron-specific Rac effector that inhibits Pak1 activity. Nature 395, 194-198   DOI
16 Hernandez P, Lee G, Sjoberg M and Maccioni RB (2009) Tau phosphorylation by cdk5 and Fyn in response to amyloid peptide Abeta (25-35): involvement of lipid rafts. J Alzheimers Dis 16, 149-156   DOI
17 Chen MC, Lin H, Hsu FN, Huang PH, Lee GS and Wang PS (2010) Involvement of cAMP in nerve growth factor-triggered p35/Cdk5 activation and differentiation in PC12 cells. Am J Physiol Cell Physiol 299, C516-C527   DOI
18 Ridley AJ (2006) Rho GTPases and actin dynamics in membrane protrusions and vesicle trafficking. Trends Cell Biol 16, 522-529   DOI
19 Ben Haim L, Ceyzeriat K, Carrillo-de Sauvage MA et al (2015) The JAK/STAT3 pathway is a common inducer of astrocyte reactivity in Alzheimer's and Huntington's diseases. J Neurosci 35, 2817-2829   DOI
20 Owen R and Gordon-Weeks PR (2003) Inhibition of glycogen synthase kinase 3beta in sensory neurons in culture alters filopodia dynamics and microtubule distribution in growth cones. Mol Cell Neurosci 23, 626-637   DOI
21 Nagao T, Kurosu T, Umezawa Y et al (2014) Proliferation and survival signaling from both Jak2-V617F and Lyn involving GSK3 and mTOR/p70S6K/4EBP1 in PVTL-1 cell line newly established from acute myeloid leukemia transformed from polycythemia vera. PLoS One 9, e84746   DOI
22 Eom TY and Jope RS (2009) Blocked inhibitory serine-phosphorylation of glycogen synthase kinase-3alpha/beta impairs in vivo neural precursor cell proliferation. Biol Psychiatry 66, 494-502   DOI
23 Lee JH and Kim KT (2004) Induction of cyclin-dependent kinase 5 and its activator p35 through the extracellular-signal-regulated kinase and protein kinase A pathways during retinoic-acid mediated neuronal differentiation in human neuroblastoma SK-N-BE(2)C cells. J Neurochem 91, 634-647   DOI
24 Kim SY, Han YM, Oh M et al (2015) DUSP4 regulates neuronal differentiation and calcium homeostasis by modulating ERK1/2 phosphorylation. Stem Cells Dev 24, 686-700   DOI
25 Thomas SM and Brugge JS (1997) Cellular functions regulated by Src family kinases. Annu Rev Cell Dev Biol 13, 513-609   DOI
26 Leonard WJ and O'Shea JJ (1998) Jaks and STATs: biological implications. Annu Rev Immunol 16, 293-322   DOI
27 Ram PA and Waxman DJ (1997) Interaction of growth hormone-activated STATs with SH2-containing phosphotyrosine phosphatase SHP-1 and nuclear JAK2 tyrosine kinase. J Biol Chem 272, 17694-17702   DOI
28 Ihle JN and Gilliland DG (2007) Jak2: normal function and role in hematopoietic disorders. Curr Opin Genet Dev 17, 8-14   DOI
29 Sandberg EM, Wallace TA, Godeny MD, VonDerLinden D and Sayeski PP (2004) Jak2 tyrosine kinase: a true jak of all trades? Cell Biochem Biophys 41, 207-232   DOI
30 Duan Z, Bradner JE, Greenberg E et al (2006) SD-1029 inhibits signal transducer and activator of transcription 3 nuclear translocation. Clin Cancer Res 12, 6844-6852   DOI
31 Miyamoto Y, Yamauchi J and Tanoue A (2008) Cdk5 phosphorylation of WAVE2 regulates oligodendrocyte precursor cell migration through nonreceptor tyrosine kinase Fyn. J Neurosci 28, 8326-8337   DOI
32 Kong X, Gong Z, Zhang L et al (2019) JAK2/STAT3 signaling mediates IL-6-inhibited neurogenesis of neural stem cells through DNA demethylation/methylation. Brain Behav Immun 79, 159-173   DOI
33 Spittaels K, Van den Haute C, Van Dorpe J et al (2002) Neonatal neuronal overexpression of glycogen synthase kinase-3 beta reduces brain size in transgenic mice. Neuroscience 113, 797-808   DOI
34 Seng S, Avraham HK, Jiang S, Venkatesh S and Avraham S (2006) KLHL1/MRP2 mediates neurite outgrowth in a glycogen synthase kinase 3beta-dependent manner. Mol Cell Biol 26, 8371-8384   DOI
35 Aspenstrom P (1999) The Rho GTPases have multiple effects on the actin cytoskeleton. Exp Cell Res 246, 20-25   DOI