Kaushansky K
Department of Medicine, University of California, San Diego, La Jolla, CA 92093-0671, USA.
J Thromb Haemost. 2009 Jul;7 Suppl 1:235-8. doi: 10.1111/j.1538-7836.2009.03419.x.
The molecular 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 1alpha and the homeobox proteins HOXB4 and HOXA9, and a number that are reduced, including glycogen synthase kinase 3alpha 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.
调节血小板生成的分子途径正越来越为人所了解。血小板生成素与其受体（原癌基因c-Mpl的产物）结合后，会激活多种促进细胞存活、增殖和分化的第二信使。其中研究得最为深入的是转录信号转导子和激活子、磷脂酰肌醇-3-激酶以及丝裂原活化蛋白激酶。这些第二介质激活的其他信号包括雷帕霉素哺乳动物靶蛋白、β-连环蛋白、缺氧诱导因子1α以及同源框蛋白HOXB4和HOXA9，还有一些信号减少，包括糖原合酶激酶3α和叉头蛋白FOXO3家族。最近，已经确定了一些使血小板生成素信号关闭的信号通路，这是避免不受控制的骨髓增殖所必需的一步，这些信号通路包括磷酸酶PTEN、SHP1和SHIP1、细胞因子信号传导抑制因子以及c-Mpl表面表达的下调。本综述将聚焦于正常和肿瘤性造血过程中的这些途径。
