CAJ | 학술논문

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.
NOK능격활포함JAK-STAT신호통로재내적다충촉세포유사분렬신호통로.연구발현,재인배신세포(HEK293T)중,NOK여STAT3구유직접적상호작용.진일보적실험표명,NOK능동STAT3단백제라선결구역급c단결구역외적기타4개결구역발생상호작용,이NOK적포내구칙개도료NOK동STAT3적상호작용.동시,면역공침정실험현시,NOK능여JAK2발생상호작용.중요적시,공동표체NOK여JAK2단백대STAT3신호통로능산생일충비상현저적협동격활작용,단당공동표체NOK화JAK2적격매활성결실돌변체시,병불산생저충협동격활효응.종상,실험결과현시,NOK가능동STAT3화JAK2형성일개복합물,통과JAK2의뢰성방식격활STAT3신호통로.
Novel oneogene 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 physicallyinteracted 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-immtmoprecipitate 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.