MK2 (p38^MAPK-activated protein kinase 2) is essential for tumor necrosis factor (TNF) biosynthesis, mainly operating by post-transcriptional regulation. Deletion of the gene encoding MK2 strongly reduced serum TNF and protected against endotoxic shock, demonstrating the positive role of p38^MAPK/MK2 in TNF signaling at the level of ligand expression. Recent evidence indicates that MK2 directly phosphorylates the TNF receptor interactor RIPK1 and suppresses its activity, thereby limiting TNF-mediated apoptosis and necroptosis – pointing to a more complex, double-edged role of MK2 in TNF signaling. In addition, novel MK2 substrates have emerged in the DNA damage response, autophagy, and obesity, making MK2 a multifunctional kinase at the crossroads of stress response and cell death. We therefore propose a more general role of p38^MAPK/MK2 signaling in the timely coordinated onset and resolution of inflammation and beyond.

MK2（p38 ^MAPK激活的蛋白激酶2）对于肿瘤坏死因子（TNF）的生物合成至关重要，主要通过转录后调控来发挥作用。删除编码MK2的基因可大大降低血清TNF并保护其免受内毒素性休克，证明p38 ^MAPK的积极作用/ MK2在TNF信号通路中的配体表达水平。最近的证据表明，MK2直接使TNF受体相互作用因子RIPK1磷酸化并抑制其活性，从而限制TNF介导的细胞凋亡和坏死病-指出MK2在TNF信号传导中具有更为复杂的双刃作用。另外，在DNA损伤反应，自噬和肥胖中出现了新型的MK2底物，使MK2成为应激反应和细胞死亡十字路口的多功能激酶。因此，我们提出了p38 ^MAPK / MK2信号传导在炎症及其他疾病的及时协调发作和消退中的更一般的作用。