Shattil S J, Leavitt A D
Department of Vascular Biology, Scripps Research Institute, La Jolla, CA 92037, USA.
Thromb Haemost. 2001 Jul;86(1):259-65.
Integrin alphaIIbbeta3 mediates key platelet adhesive responses during hemostasis and thrombosis. Adhesive ligand binding to alphaIIbbeta3 is regulated by "inside-out" signals, while adhesion-dependent cytoskeletal events are regulated by "outside-in" signals from alphaIIbbeta3. Currently, the molecular basis of bidirectional alphaIIbbeta3 signaling is incompletely understood. The functional assessment of integrin signaling pathways in nucleated cells has been facilitated by techniques such as viral transduction which enable expression of dominant-active and dominant-inhibitory gene products. This approach cannot be used with anucleate platelets. However, recent advances in the ability to expand human and murine megakaryocytes from hematopoietic stem cells provide a tractable and genetically manipulatable system for studies of alphaIIbbeta3 signaling. This overview will discuss some of the advantages and limitations of this approach and provide examples of its utility. Thus, in addition to their intrinsic value for understanding hematopoiesis and platelet formation, primary megakaryocytes represent a model system complementary to platelets for unraveling the remaining mysteries of alphaIIbbeta3 signaling.
整合素αIIbβ3在止血和血栓形成过程中介导关键的血小板黏附反应。黏附配体与αIIbβ3的结合受“由内向外”信号调控，而依赖黏附的细胞骨架事件则受来自αIIbβ3的“由外向内”信号调控。目前，双向αIIbβ3信号传导的分子基础尚未完全阐明。通过病毒转导等技术可以促进对有核细胞中整合素信号通路的功能评估，这些技术能够表达显性激活和显性抑制基因产物。这种方法不能用于无核血小板。然而，从造血干细胞扩增人和小鼠巨核细胞的能力方面的最新进展，为研究αIIbβ3信号传导提供了一个易于处理且可进行基因操作的系统。本综述将讨论这种方法的一些优点和局限性，并提供其应用实例。因此，除了在理解造血和血小板形成方面的内在价值外，原代巨核细胞代表了一个与血小板互补的模型系统，用于解开αIIbβ3信号传导的其余谜团。
