Depletion of Janus kinase-2 promotes neuronal differentiation of mouse embryonic stem cells
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Janus kinase 2 (JAK2), a non-receptor tyrosine kinase, is a criticalcomponent of cytokine and growth factor signaling pathwaysregulating hematopoietic cell proliferation. JAK2 mutations areassociated with multiple myeloproliferative neoplasms. Althoughphysiological and pathological functions of JAK2 in hematopoietictissues are well-known, such functions of JAK2 in thenervous system are not well studied yet. The present study demonstratedthat JAK2 could negatively regulate neuronal differentiationof mouse embryonic stem cells (ESCs). Depletion ofJAK2 stimulated neuronal differentiation of mouse ESCs andactivated glycogen synthase kinase 3ꞵ, Fyn, and cyclin-dependentkinase 5. Knockdown of JAK2 resulted in accumulation of GTPboundRac1, a Rho GTPase implicated in the regulation of cytoskeletaldynamics. These findings suggest that JAK2 might negativelyregulate neuronal differentiation by suppressing the GSK-3β/Fyn/CDK5 signaling pathway responsible for morphological maturation.
Abstract
Janus kinase 2 (JAK2), a non-receptor tyrosine kinase, is a criticalcomponent of cytokine and growth factor signaling pathwaysregulating hematopoietic cell proliferation. JAK2 mutations areassociated with multiple myeloproliferative neoplasms. Althoughphysiological and pathological functions of JAK2 in hematopoietictissues are well-known, such functions of JAK2 in thenervous system are not well studied yet. The present study demonstratedthat JAK2 could negatively regulate neuronal differentiationof mouse embryonic stem cells (ESCs). Depletion ofJAK2 stimulated neuronal differentiation of mouse ESCs andactivated glycogen synthase kinase 3ꞵ, Fyn, and cyclin-dependentkinase 5. Knockdown of JAK2 resulted in accumulation of GTPboundRac1, a Rho GTPase implicated in the regulation of cytoskeletaldynamics. These findings suggest that JAK2 might negativelyregulate neuronal differentiation by suppressing the GSK-3β/Fyn/CDK5 signaling pathway responsible for morphological maturation.
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