Molecular mechanisms of thrombopoietin signaling
Molecular mechanisms of thrombopoietin signaling
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DOI：
10.1111/j.1538-7836.2009.03419.x
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发表时间：
2009-07-01
影响因子：
10.4
通讯作者：
Kaushansky, K.
中科院分区：
文献类型：
--
作者：
Kaushansky, K.
调节血小板生成的分子途径越来越被人们所了解。血小板生成素与其受体（c-Mpl原癌基因的产物）结合后，激活许多促进细胞存活、增殖和分化的第二信使。其中最好的研究是信号转导和转录激活剂，磷酸肌醇-3-激酶，有丝分裂原活化蛋白激酶。由这些次级介质激活的其他信号包括雷帕霉素、β-连环蛋白、缺氧诱导因子1 α和同源框蛋白HOXB 4和HOXA 9的哺乳动物靶点，以及一些减少的信号，包括糖原合成酶激酶3 α和FOXO 3家族的叉头蛋白。最近，已经鉴定了许多信号传导途径，其关闭血小板生成素信号，这是避免不受控制的骨髓增殖所必需的步骤，并且包括磷酸酶PTEN、SHP 1和SHIP 1，细胞因子信号传导的抑制剂，以及c-Mpl的表面表达的下调。本文将重点介绍正常和肿瘤性造血中的这些途径。
Themolecular pathways that regulate thrombopoiesis are becoming increasingly understood. Upon binding to its receptor, the product of the c-Mpl proto-oncogene, thrombopoietin activates a number of secondary messengers that promote cell survival, proliferation and differentiation. Amongst the best studied are the signal transducers and activators of transcription, phosphoinositol-3-kinase, and the mitogen-activated protein kinases. Additional signals activated by these secondary mediators include mammalian target of rapamycin, beta-catenin, hypoxia-inducible factor 1 alpha and the homeobox proteins HOXB4 and HOXA9, and a number that are reduced, including glycogen synthase kinase 3 alpha and the FOXO3 family of forkhead proteins. More recently, a number of signaling pathways have been identified that turn the thrombopoietin signal off a step necessary to avoid uncontrolled myeloproliferation, and include the phosphatases PTEN, SHP1 and SHIP1, the suppressors of cytokine signaling, and down-modulation of surface expression of c-Mpl. This review will focus on these pathways in normal and neoplastic hematopoiesis.