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首页> 外文期刊>Molecular and Cellular Biology >Tyrosine 763 of the murine granulocyte colony-stimulating factor receptor mediates Ras-dependent activation of the JNK/SAPK mitogen-activated protein kinase pathway.
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Tyrosine 763 of the murine granulocyte colony-stimulating factor receptor mediates Ras-dependent activation of the JNK/SAPK mitogen-activated protein kinase pathway.

机译：鼠粒细胞集落刺激因子受体的酪氨酸763介导JNK / SAPK丝裂原激活的蛋白激酶途径的Ras依赖性激活。

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摘要

The receptor for granulocyte colony-stimulating factor (G-CSF) can mediate differentiation and proliferation of hemopoietic cells. A proliferative signal is associated with activation of the ERK mitogen-activated protein kinase (MAPK) pathway. To determine whether other MAPK pathways are activated by G-CSF signalling, we have investigated activation of JNK/SAPK in cells proliferating in response to G-CSF. Here we show that G-CSF and interleukin-3 activate JNK/SAPK in two hemopoietic cell lines. The region of the G-CSF receptor required for G-CSF-induced JNK/SAPK activation is located within the C-terminal 68 amino acids of the cytoplasmic domain, which contains Tyr 763. Mutation of Tyr 763 to Phe completely blocks JNK/SAPK activation. However, the C-terminal 68 amino acids are not required for ERK2 activation. We show that activation of JNK/SAPK, like that of ERK2, is dependent on Ras but that higher levels of Ras-GTP are associated with activation of JNK/SAPK than with activation of ERK2. Two separate functional regions of the G-CSF receptor contribute to activation of Ras. The Y763F mutation reduces G-CSF-induced Ras activation from 30 to 35% Ras-GTP to 10 to 13% Ras-GTP. Low levels of Ras activation (10 to 13% Ras-GTP), which are sufficient for ERK2 activation, require only the 100 membrane-proximal amino acids. High levels of Ras-GTP provided by expression of oncogenic Ras are not sufficient to activate JNK/SAPK. An additional signal, also mediated by Tyr 763, is required for activation of JNK/SAPK.
机译：粒细胞集落刺激因子（G-CSF）的受体可以介导造血细胞的分化和增殖。增殖信号与ERK丝裂原激活的蛋白激酶（MAPK）途径的激活有关。为了确定其他MAPK途径是否被G-CSF信号激活，我们研究了在响应G-CSF增殖的细胞中JNK / SAPK的激活。在这里，我们显示G-CSF和白介素3激活两种造血细胞系中的JNK / SAPK。 G-CSF诱导的JNK / SAPK激活所需的G-CSF受体区域位于胞质域的C端68个氨基酸内，其中包含Tyr763。Tyr763突变为Phe会完全阻断JNK / SAPK激活。但是，ERK2激活不需要C端68个氨基酸。我们显示，像ERK2一样，JNK / SAPK的激活也依赖于Ras，但与ERK2激活相比，更高水平的Ras-GTP与JNK / SAPK的激活相关。 G-CSF受体的两个独立的功能区有助于激活Ras。 Y763F突变将G-CSF诱导的Ras激活从30％到35％Ras-GTP降低到10％到13％Ras-GTP。低水平的Ras激活（10％至13％Ras-GTP）足以激活ERK2，仅需要100个膜近端氨基酸。致癌性Ras表达提供的高水平Ras-GTP不足以激活JNK / SAPK。 JNK / SAPK的激活还需要一个由Tyr 763介导的信号。

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