Centre for Cardiovascular Sciences, Institute for Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
J Thromb Haemost. 2010 Jan;8(1):17-26. doi: 10.1111/j.1538-7836.2009.03658.x. Epub 2009 Oct 23.
Megakaryopoiesis is a process by which bone marrow progenitor cells develop into mature megakaryocytes (MKs), which in turn produce platelets required for normal hemostasis. The mitogen-activated protein kinases (MAPKs) family comprises four main groups of proteins: extracellular signal-related kinases (ERKs) (ERK1/2 or p44/p42), ERK5, p38MAPKs (alpha, beta, gamma, delta) and c-Jun amino-terminal kinases (JNKs) (JNK 1, 2, 3). These intracellular signaling pathways play a pivotal role in many essential cellular processes including proliferation and differentiation. The purpose of this review is to summarize our current knowledge on the role of MAPKs in MKs, specifically regarding differentiation in immortalized cell lines and primary MKs. A critical role of the MEK (MAPK kinase)-ERK1/2 pathway in MK development has been demonstrated although the details remain controversial. There is at present no functional evidence for a role of p38MAPKs whereas the role of JNKs and ERK5 in MK development is not known. Characterization of these molecular event cascades remains crucial for the understanding of the megakaryopoiesis process.
巨核细胞生成是骨髓祖细胞发育为成熟巨核细胞（MK）的过程，MK 又会产生正常止血所需的血小板。丝裂原激活的蛋白激酶（MAPK）家族由四个主要蛋白群组成：细胞外信号相关激酶（ERK）（ERK1/2 或 p44/p42）、ERK5、p38MAPK（α、β、γ、δ）和 c-Jun 氨基末端激酶（JNK）（JNK1、2、3）。这些细胞内信号通路在许多基本的细胞过程中起着关键作用，包括增殖和分化。本综述旨在总结我们目前对 MAPK 在 MK 中的作用的认识，特别是关于永生化细胞系和原代 MK 分化的作用。MEK（MAPK 激酶）-ERK1/2 通路在 MK 发育中的关键作用已得到证实，尽管其细节仍存在争议。目前尚无 p38MAPK 作用的功能证据，而 JNK 和 ERK5 在 MK 发育中的作用尚不清楚。这些分子事件级联的特征对于理解巨核细胞生成过程仍然至关重要。
