NOK通过JAK2依赖性方式激活STAT3信号通路(英文)

NOK Activates STAT3 Signaling by a JAK2-Dependent Mechanism

NOK能激活包含JAK-STAT信号通路在内的多种促细胞有丝分裂信号通路.研究发现,在人胚肾细胞(HEK293T)中,NOK与STAT3具有直接的相互作用.进一步的实验表明,NOK能同STAT3蛋白除螺旋结构域及C端结构域外的其他4个结构域发生相互作用,而NOK的胞内区则介导了NOK同STAT3的相互作用.同时,免疫共沉淀实验显示,NOK能与JAK2发生相互作用.重要的是,共同表达NOK与JAK2蛋白对STAT3信号通路能产生一种非常显著的协同激活作用,但当共同表达NOK和JAK2的激酶活性缺失突变体时,并不产生这种协同激活效应.综上,实验结果显示,NOK可能同STAT3和JAK2形成一个复合物,通过JAK2依赖性方式激活STAT3信号通路.

Novel oncogene with kinase-domain （NOK） can activate multiple mitogenic signaling pathways including the janus kinases （JAK） and signal transducer and activator of transcription proteins （STAT）. It was showed that NOK specifically and physically interacted with STAT3 in human embryo kidney 293T （HEK293T） cells. In addition, NOK could directly interact with most of the STAT3 subdomains except coiled-coil and C-terminal domains. Removing ectodomain and transmembrane domain of NOK markedly enhanced its intermolecular interaction with STAT3. Also, NOK could co-immunoprecipitate with JAK2 in vivo. Importantly, co-expression of NOK and JAK2 produced a synergistic effect on NOK-mediated STAT3 activation, while inactivating the kinase domain of JAK2 completely prevented this synergistic effect. Overall, the results indicated that NOK might complex with both STAT3 and JAK2 and activate STAT3 signaling by a JAK2-dependent mechanism.