Activation of Akt kinase by granulocyte colony-stimulating factor (G-CSF): evidence for the role of a tyrosine kinase activity distinct from the janus kinases
Activation of Akt kinase by granulocyte colony-stimulating factor (G-CSF): evidence for the role of a tyrosine kinase activity distinct from the janus kinases
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DOI：
10.1182/blood.v95.5.1656.005k29_1656_1662
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发表时间：
2000-03-01
期刊：
影响因子：
20.3
通讯作者：
Larner, AC
中科院分区：
文献类型：
--
作者：
Dong, F;Larner, AC
丝氨酸/苏氨酸激酶 Akt 的激活已被证明是生长因子和细胞因子刺激细胞存活的关键成分。尽管 Akt 的一些直接上游激活剂已被定义，但酪氨酸激酶在 Akt 激活中的作用尚不清楚。粒细胞集落刺激因子 (G-CSF) 调节中性粒细胞的增殖、分化和存活。 G-CSF 与其细胞表面受体结合后，通过刺激多个信号级联反应来发挥作用。 Jak (Janus) 和 Src 家族的酪氨酸激酶均通过细胞与 G-CSF 的孵育而受到刺激。在本报告中，我们表明细胞的 G-CSF 刺激会导致 Akt 的激活。G-CSF 受体胞质结构域的近膜 55 个氨基酸足以介导 Akt 激活。然而，AM 的激活似乎受到该受体的 98 个氨基酸的羧基末端区域的下调，该区域已被证明在一些与严重先天性中性粒细胞减少症相关的急性髓系白血病患者中被截短。此外，我们证明 G-CSF 诱导的 AM 激活需要 Src 家族激酶的活性，但可以清楚地与 G-CSF 刺激的 Jak 激酶对 Stats（信号转导子和转录子激活子）的激活分离。因此，Jak/Stat 的细胞因子激活和其他信号级联可以在功能上分开，（C）2000，美国血液学会。
Activation of the serine/threonine kinase Akt has been shown to be a critical component for growth factor and cytokine stimulation of cell survival. Although some of the immediate upstream activators of Akt have been defined, the roles of tyrosine kinases in the activation of Akt are not well delineated. Granulocyte colony-stimulating factor (G-CSF) regulates the proliferation, differentiation, and survival of neutrophilic granulocytes. G-CSF exerts its actions by stimulating several signaling cascades after binding its cell surface receptor. Both Jak (Janus) and Src families of tyrosine kinases are stimulated by incubation of cells with G-CSF, In this report, we show that G-CSF stimulation of cells leads to activation of Akt, The membrane-proximal 55 amino acids of the G-CSF receptor cytoplasmic domain are sufficient for mediating Akt activation. However, activation of AM appears to be downregulated by the receptor's carboxy-terminal region of 98 amino acids, a region that has been shown to be truncated in some patients with acute myeloid leukemia associated with severe congenital neutropenia. Furthermore, we demonstrate that G-CSF-induced activation of AM requires the activities of Src family kinases but can be clearly dissociated from G-CSF-stimulated activation of Stats (signal transducers and activators of transcripton) by the Jak kinases, Thus, cytokine activation of the Jak/Stat and other signaling cascades can be functionally separated, (C) 2000 by The American Society of Hematology.