Joshi Sonali, Platanias Leonidas C
Robert H. Lurie Comprehensive Cancer Center and Division of Hematology-Oncology, Northwestern University Medical School, and Jesse Brown VA, Medical Center, Chicago, IL ; Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, TX.
Biomol Concepts. 2012 Apr;3(2):127-139. doi: 10.1515/bmc-2011-0057.
The kinases Mnk1 and Mnk2 are activated downstream of the p38 MAPK and MEK/ERK signaling pathways. Extensive work over the years has shown that these kinases control phosphorylation of the eukaryotic initiation factor 4E (eIF4E) and regulate engagement of other effector elements, including hnRNPA1 and PSF. Mnk kinases are ubiquitously expressed and play critical roles in signaling for various cytokine receptors, while there is emerging evidence that they have important functions as mediators of pro-inflammatory cytokine production. In this review the mechanisms of activation of MNK pathways by cytokine receptors are addressed and their roles in diverse cytokine-dependent biological processes are reviewed. The clinical-translational implications of such work and the relevance of future development of specific MNK inhibitors for the treatment of malignancies and auto-immune disorders are discussed.
激酶Mnk1和Mnk2在p38丝裂原活化蛋白激酶（MAPK）和MEK/细胞外信号调节激酶（ERK）信号通路的下游被激活。多年来的大量研究表明，这些激酶控制真核生物起始因子4E（eIF4E）的磷酸化，并调节包括异质性核糖核蛋白A1（hnRNPA1）和多聚嘧啶序列结合蛋白（PSF）在内的其他效应元件的参与。Mnk激酶在全身广泛表达，在多种细胞因子受体的信号传导中起关键作用，同时越来越多的证据表明它们作为促炎细胞因子产生的介质具有重要功能。在这篇综述中，我们阐述了细胞因子受体激活MNK通路的机制，并综述了它们在多种细胞因子依赖性生物学过程中的作用。我们还讨论了此类研究的临床转化意义，以及未来开发特异性Mnk抑制剂用于治疗恶性肿瘤和自身免疫性疾病的相关性。
