Signaling Pathways That Regulate Normal and Aberrant Red Blood Cell Development.
Signaling Pathways That Regulate Normal and Aberrant Red Blood Cell Development.
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调节正常和异常红细胞发育的信号通路。
DOI：
10.3390/genes12101646
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发表时间：
2021-10-19
期刊：
影响因子：
3.5
通讯作者：
Sakamoto KM
中科院分区：
文献类型：
--
作者：
Wilkes MC;Shibuya A;Sakamoto KM
血细胞发育是通过内在的基因调控和局部因素，包括微环境和细胞因子来调节的。造血干细胞和祖细胞向成熟红细胞的分化依赖于这些细胞因子与其同源受体的结合和刺激，以及它们启动的信号级联反应。其中许多途径包括通过磷酸化多个底物使信号多样化，并通过磷酸化每个底物的多个拷贝放大信号的激酶。事实上，许多这些细胞因子的合成受到许多信号通路的调节，包括磷脂酰肌醇3-激酶(PI3K)-、细胞外信号相关激酶(ERK-)-和p38激酶依赖的通路。因此，激酶在红细胞生成调节细胞因子的上游和下游都起作用。虽然许多细胞因子都有很好的特性，但负责适当诱导和响应这些细胞因子的激酶网络的细微差别成员仍然缺乏明确的定义。在这里，我们将研究红细胞生成所需的激酶信号级联反应，并强调重要性、复杂性、有待表征的巨大数量以及伴随着我们对健康和疾病状态下的红系染色体的全面理解而产生的治疗潜力。
Blood cell development is regulated through intrinsic gene regulation and local factors including the microenvironment and cytokines. The differentiation of hematopoietic stem and progenitor cells (HSPCs) into mature erythrocytes is dependent on these cytokines binding to and stimulating their cognate receptors and the signaling cascades they initiate. Many of these pathways include kinases that can diversify signals by phosphorylating multiple substrates and amplify signals by phosphorylating multiple copies of each substrate. Indeed, synthesis of many of these cytokines is regulated by a number of signaling pathways including phosphoinositide 3-kinase (PI3K)-, extracellular signal related kinases (ERK)-, and p38 kinase-dependent pathways. Therefore, kinases act both upstream and downstream of the erythropoiesis-regulating cytokines. While many of the cytokines are well characterized, the nuanced members of the network of kinases responsible for appropriate induction of, and response to, these cytokines remains poorly defined. Here, we will examine the kinase signaling cascades required for erythropoiesis and emphasize the importance, complexity, enormous amount remaining to be characterized, and therapeutic potential that will accompany our comprehensive understanding of the erythroid kinome in both healthy and diseased states.
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通讯作者：
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