原发性家族性和先天性红细胞增多症发病机制研究进展。
Advances in understanding the pathogenesis of primary familial and congenital polycythaemia.
机构信息
Department of Cell Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9039, USA.
出版信息
Br J Haematol. 2010 Mar;148(6):844-52. doi: 10.1111/j.1365-2141.2009.08069.x. Epub 2010 Jan 20.
Abstract
Primary familial and congenital polycythemia (PFCP) is an autosomal-dominant proliferative disorder characterized by erythrocytosis and hypersensitivity of erythroid progenitors to erythropoietin (Epo). Several lines of evidence suggest a causal role of truncated erythropoietin receptor (EpoR) in this disease. In this review, we discuss PFCP in the context of erythrocytosis and EpoR signalling. We focus on recent studies describing mechanisms underlying Epo-dependent EpoR down-regulation. One mechanism depends on internalization mediated through the p85 regulatory subunit of the Phosphoinositide 3-Kinase, and the other utilizes ubiquitin-based proteasomal degradation. Truncated PFCP EpoRs are not properly down-regulated upon stimulation, underscoring the importance of these mechanisms in the pathogenesis of PFCP.
摘要
原发性家族性先天性红细胞增多症（PFCP）是一种常染色体显性增生性疾病，其特征为红细胞增多和红系祖细胞对促红细胞生成素（Epo）的敏感性增加。有几条证据表明，截短的促红细胞生成素受体（EpoR）在这种疾病中起因果作用。在这篇综述中，我们将在红细胞增多症和 EpoR 信号的背景下讨论 PFCP。我们重点介绍了最近描述 Epo 依赖性 EpoR 下调机制的研究。一种机制依赖于通过 Phosphoinositide 3-Kinase 的 p85 调节亚基介导的内化，另一种机制利用基于泛素的蛋白酶体降解。刺激后截短的 PFCP EpoR 不能适当下调，这突出了这些机制在 PFCP 发病机制中的重要性。
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