UMR U978 Inserm/Université Paris 13, UFR SMBH, Bobigny, France.
Arch Immunol Ther Exp (Warsz). 2012 Dec;60(6):415-29. doi: 10.1007/s00005-012-0194-x. Epub 2012 Sep 19.
The development and function of blood cells are regulated by specific growth factors/cytokines and their receptors' signaling pathways. In this way, these factors influence cell survival, proliferation and differentiation of hematopoietic cells. Central to this positive and/or negative control are the adaptor proteins. Since their identification 10 years ago, members of the Lnk adaptor protein family have proved to be important activators and/or inhibitors in the hematopoietic, immune and vascular system. In particular, the generation of animal and cellular models for the Lnk and APS proteins has helped establish the physiological role of these molecules through the identification of their specific signaling pathways and the characterization of their binding partners. Moreover, the recent identification of mutations in the LNK gene in myeloproliferative disorders, as well as the correlation of a single nucleotide polymorphism on LNK with hematological, immune and vascular diseases have suggested its involvement in the pathophysiology of these malignancies. The latter findings have thus raised the possibility of addressing Lnk signaling for the treatment of certain human diseases. This review therefore describes the pathophysiological role of this adaptor protein in hematological malignancies and the potential benefits of Lnk therapeutic targeting.
血细胞的发育和功能受特定生长因子/细胞因子及其受体信号通路的调节。通过这种方式，这些因子影响造血细胞的存活、增殖和分化。这种正调控和/或负调控的核心是衔接蛋白。自 10 年前发现衔接蛋白以来，Lnk 衔接蛋白家族的成员已被证明是造血、免疫和血管系统中的重要激活剂和/或抑制剂。特别是，通过鉴定 Lnk 和 APS 蛋白的特定信号通路及其结合伙伴，动物和细胞模型的产生有助于确定这些分子的生理作用。此外，最近在骨髓增生性疾病中发现 LNK 基因的突变，以及 LNK 上的单核苷酸多态性与血液、免疫和血管疾病的相关性表明，它参与了这些恶性肿瘤的病理生理学。这些发现使人们有可能针对 Lnk 信号通路治疗某些人类疾病。因此，本综述描述了这种衔接蛋白在血液恶性肿瘤中的病理生理学作用以及 Lnk 治疗靶向的潜在益处。
