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KMID : 0624620210540120626
BMB Reports
2021 Volume.54 No. 12 p.626 ~ p.631
Depletion of Janus kinase-2 promotes neuronal differentiation of mouse embryonic stem cells
Oh Mi-Hee

Kim Sun-Young
Byun Jeong-Su
Lee Seon-Ha
Kim Won-Kon
Oh Kyoung-Jin
Lee Eun-Woo
Lee Sang-Chul
Han Baek-Soo
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 3?, Fyn, and cyclin-dependent kinase 5. Knockdown of JAK2 resulted in accumulation of GTPbound 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-3¥â/Fyn/CDK5 signaling pathway responsible for morphological maturation.
KEYWORD
Cyclin-dependent kinase 5 (CDK5), Embryonic stem cell, Glycogen synthase kinase 3¥â (GSK3 ¥â), Janus kinase-2 (JAK2), Neurogenesis, Neuronal differentiation
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