JAK2 tyrosine kinase inhibitor tyrphostin AG490 downregulates the mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription (STAT) pathways and induces apoptosis in myeloma cells
JAK2 tyrosine kinase inhibitor tyrphostin AG490 downregulates the mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription (STAT) pathways and induces apoptosis in myeloma cells
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DOI：
10.1046/j.1365-2141.2000.02127.x
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发表时间：
2000-06-01
影响因子：
6.5
通讯作者：
Klein, B
中科院分区：
文献类型：
--
作者：
De Vos, J;Jourdan, M;Klein, B
白细胞介素6（IL-6）家族的细胞因子，激活信号转导gp 130，是人类多发性骨髓瘤（MM）细胞的主要生存和生长因子。gp 130的信号转导涉及Janus酪氨酸激酶（JAK）JAK 1、JAK 2和Tyk 2，然后是下游效应子，包括信号转导子和转录激活子3（STAT 3）和促分裂原活化蛋白激酶（MAPK）途径。我们评估了JAK 2抑制剂tyrphostin AG 490对MM细胞的作用。我们发现，AG 490抑制细胞增殖和诱导凋亡的IL-6依赖性MM细胞系。JAK 2激酶活性、ERK 2和STAT 3磷酸化受到抑制。这些结果表明，在JAK水平上化学阻断gp 130信号通路可能是MM的相关治疗方法。
Cytokines of the interleukin 6 (IL-6) family, which activates the signal transducer gp130, are major survival and growth factors for human multiple myeloma (MM) cells. The signal transduction of gp130 involves the Janus tyrosine kinases (JAK) JAK1, JAK2 and Tyk2 and then the downstream effectors comprising the signal transducer and activator of transcription 3 (STAT3) and mitogen-activated protein kinase (MAPK) pathways. We evaluated the effects of the JAK2 inhibitor tyrphostin AG490 on MM cells. We found that AG490 suppressed cell proliferation and induced apoptosis in IL-6-dependent MM cell lines. JAK2 kinase activity, ERK2 and STAT3 phosphorylation were inhibited. These results suggest that the chemical blocking of the gp130 signalling pathway at the JAK level could be a relevant therapeutic approach to MM.