rel Is rapidly tyrosine-phosphorylated following granulocyte-colony stimulating factor treatment of human neutrophils.
rel Is rapidly tyrosine-phosphorylated following granulocyte-colony stimulating factor treatment of human neutrophils.
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DOI：
10.1016/s0021-9258(17)37699-8
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发表时间：
1994-02
期刊：
影响因子：
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通讯作者：
B. Druker;M. Neumann;Keiko Okuda;B. Franza;James D. Griffin
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文献类型：
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作者：
B. Druker;M. Neumann;Keiko Okuda;B. Franza;James D. Griffin
用粒细胞集落刺激因子 (G-CSF) 刺激中性粒细胞可增强呼吸爆发、延长生存时间并增加肿瘤细胞杀伤力。 G-CSF 的作用是通过与特定的高亲和力受体结合来介导的。 G-CSF受体缺乏内在的酪氨酸激酶活性，但受体的激活会导致酪氨酸激酶活性的快速诱导。中性粒细胞制备的全细胞裂解物的抗磷酸酪氨酸免疫印迹表明，G-CSF 快速诱导相对分子质量为 80 kDa 的蛋白质显着的酪氨酸磷酸化。使用单特异性抗体，80 kDa 酪氨酸磷酸化蛋白已被证明是 p80c-rel，一种原癌基因，属于包括 NF-kB 在内的转录调节因子家族。 p80c-rel酪氨酸磷酸化的诱导对于G-CSF来说是独特的，因为粒细胞-巨噬细胞集落刺激因子也刺激嗜中性粒细胞并诱导酪氨酸磷酸化，但不会导致p80c-rel酪氨酸磷酸化。 p80c-rel 酪氨酸磷酸化的后果尚不清楚；然而，酪氨酸磷酸化的 p80c-rel 能够与 DNA 结合，并且 G-CSF 刺激会导致与 DNA 结合的 p80c-rel 量增加。这些结果表明，G-CSF 刺激后中性粒细胞中发生的第一个生化事件，即酪氨酸激酶的激活，直接导致 p80c-rel 的酪氨酸磷酸化。因此，G-CSF 激活的酪氨酸激酶似乎直接将信号转导至充当转录调节因子的蛋白质。
Stimulation of neutrophils with granulocyte-colony stimulating factor (G-CSF) results in an enhanced respiratory burst, prolonged survival, and increased tumor cell killing. The effects of G-CSF are mediated by binding to specific, high affinity receptors. G-CSF receptors lack intrinsic tyrosine kinase activity, but activation of the receptor results in the rapid induction of tyrosine kinase activity. Antiphosphotyrosine immunoblots of whole cell lysates prepared from neutrophils show that the G-CSF rapidly induces prominent tyrosine phosphorylation of a protein of a relative molecular mass of 80 kDa. Using monospecific antibodies, the 80-kDa tyrosine-phosphorylated protein has been shown to be p80c-rel, a proto-oncogene belonging to a family of transcriptional regulators which include NF-kB. The induction of tyrosine phosphorylation of p80c-rel was unique to G-CSF in that granulocyte-macrophage colony stimulating factor which also stimulates neutrophils and induces tyrosine phosphorylation does not result in tyrosine phosphorylation of p80c-rel. The consequences of p80c-rel tyrosine phosphorylation are not yet known; however, tyrosine-phosphorylated p80c-rel is capable of binding to DNA, and G-CSF stimulation results in an increase in the amount of p80c-rel which binds to DNA. These results demonstrate that one of the first biochemical events which occurs in neutrophils following G-CSF stimulation, activation of a tyrosine kinase, leads directly to the tyrosine phosphorylation of p80c-rel. Thus, the tyrosine kinase activated by G-CSF appears to directly transduce a signal to a protein which functions as a transcriptional regulator.