Buxade Maria, Parra-Palau Josep L, Proud Christopher G
Immunopathology Unit, Department of Experimental and Health Sciences, Pompeu Fabra University, Doctor Aiguader 88, 08003 Barcelona, Spain.
Front Biosci. 2008 May 1;13:5359-73. doi: 10.2741/3086.
The human MAP kinase-interacting kinases (or MAP kinase signal-integrating kinases), Mnks, comprise a group of four proteins derived from two genes (Gene symbols: MKNK1 and MKNK2) by alternative splicing. Mnk1a/b differ at their C-termini, as do Mnk2a/2b: in each case, the a-form possesses a longer C-terminal region than the b-form, which lacks the MAP kinase-binding region. The N-termini of all forms contain a polybasic region which binds importin a and the translation factor scaffold protein eukaryotic initiation factor (eIF) 4G. The catalytic domains of Mnk1a/b and Mnk2a/b share three unusual features: two short inserts and a DFD feature where other kinases have DFG. Mnk isoforms differ markedly in their activity and regulation, and in subcellular localization. The best-characterised Mnk substrate is eIF4E. The cellular role of eIF4E phosphorylation remains unclear: it may promote export of certain mRNAs from the nucleus. Other Mnk substrates bind to AU-rich elements that modulate the stability/translation of specific mRNAs. Mnks may also control production of inflammatory mediators and signaling from tyrosine kinase receptors, as well as cell proliferation or survival.
人类丝裂原活化蛋白激酶相互作用激酶（或丝裂原活化蛋白激酶信号整合激酶），即Mnks，由两个基因（基因符号：MKNK1和MKNK2）通过可变剪接产生的一组四种蛋白质组成。Mnk1a/b在其C末端存在差异，Mnk2a/2b也是如此：在每种情况下，a型具有比b型更长的C末端区域，b型缺乏丝裂原活化蛋白激酶结合区域。所有形式的N末端都包含一个多碱性区域，该区域与输入蛋白α和翻译因子支架蛋白真核起始因子（eIF）4G结合。Mnk1a/b和Mnk2a/b的催化结构域具有三个不同寻常的特征：两个短插入序列和一个在其他激酶具有DFG的位置的DFD特征。Mnk同工型在其活性、调节和亚细胞定位方面存在显著差异。最具特征的Mnk底物是eIF4E。eIF4E磷酸化的细胞作用仍不清楚：它可能促进某些mRNA从细胞核输出。其他Mnk底物与富含AU元件结合，这些元件调节特定mRNA的稳定性/翻译。Mnks还可能控制炎症介质的产生以及酪氨酸激酶受体的信号传导，以及细胞增殖或存活。
