Activation and inactivation of signal transducers and activators of transcription by ciliary neurotrophic factor in neuroblastoma cells.
Activation and inactivation of signal transducers and activators of transcription by ciliary neurotrophic factor in neuroblastoma cells.
复制标题
神经母细胞瘤细胞中睫状神经营养因子对信号转导器和转录激活剂的激活和失活。
DOI：
10.1016/s0898-6568(01)00280-7
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发表时间：
2002
影响因子：
4.8
通讯作者：
Halvorsen,StanleyW
中科院分区：
文献类型：
--
作者：
Kaur,Navjot;Wohlhueter,AnnL;Halvorsen,StanleyW
体内的神经元暴露于多种不同的生长因子和细胞因子。睫状神经营养因子（CNTF）样细胞因子的主要信号传导途径是Janus激酶（Jak）/激酶和转录因子的信号转导和转录激活因子（STAT）系统。在人细胞系（SH-SY 5 Y）中，CNTF样细胞因子激活的STAT 1和STAT 3显示酪氨酸磷酸化在0.5 h达到峰值，并在2 h内失活。受体相关酪氨酸激酶Jak 1和Jak 2的酪氨酸磷酸化在响应CNTF时表现出相似的激活和失活时间过程。STAT 1对非CNTF样细胞因子干扰素-γ（IFN-γ）的反应没有减弱。CNTF的失活不是由于CNTF受体亚基gp 130或Jak 1或Jak 2水平的降低。STAT失活被蛋白激酶阻断剂H7和酪氨酸磷酸酶阻断剂抑制，但不被蛋白激酶C、促分裂原活化蛋白激酶（MAPK）激酶、mTOR-P70/S6激酶或磷脂酰肌醇-3-激酶（PI-3激酶）抑制剂抑制。令人惊讶的是，CNTF仅引起细胞因子信号传导抑制因子SOCS-1和SOCS-3水平的轻微增加。CNTF预处理可使细胞对CNTF样细胞因子、白血病抑制因子和抑瘤素-M脱敏，但对IFN-γ不敏感。这些结果揭示了细胞因子的共享信号传导途径的复杂调节水平，其依赖于细胞和细胞因子的类型。
Neurons in vivo are exposed to a variety of different growth factors and cytokines. A principal signalling pathway for ciliary neurotrophic factor (CNTF)-like cytokines is the Janus kinase (Jak)/signal transducer and activator of transcription (STAT) system of kinases and transcription factors. In the human cell line (SH-SY5Y), STAT1 and STAT3 activation by CNTF-like cytokines showed tyrosine phosphorylation peaking at 0.5 h and inactivating within 2 h. Tyrosine phosphorylation of the receptor-associated tyrosine kinases Jak1 and Jak2 showed a similar time course of activation and inactivation in response to CNTF. The STAT1 response to the non-CNTF-like cytokine, interferon-γ (IFN-γ) did not inactivate. Inactivation to CNTF was not due to a decrease in CNTF receptor subunit gp130 or in levels of Jak1 or Jak2. STAT inactivation was inhibited by the protein kinase blocker H7 and a tyrosine phosphatase blocker, but not by inhibitors of protein kinase C, mitogen-activated protein kinase (MAPK) kinase, mTOR-P70/S6 kinase or phosphatidyl inositol-3-kinase (PI-3 kinase). Surprisingly, CNTF caused only a minor increase in levels of suppressors of cytokine signalling, SOCS-1 and SOCS-3. CNTF pretreatment desensitized the cells to the CNTF-like cytokines, leukemia inhibitory factor and oncostatin-M but not to IFN-γ. These results reveal a complex level of regulation of shared signalling pathways for cytokines that is dependent on both the type of cell and cytokine.