University of Tromsø Faculty of Health Sciences, Department of Medical Biology, Molecular Inflammation Research Group, N-9037 Tromsø, Norway.
Biol Chem. 2013 Sep;394(9):1115-32. doi: 10.1515/hsz-2013-0149.
Mitogen-activated protein kinase (MAPK) pathways are important signal transduction pathways that control pivotal cellular processes including proliferation, differentiation, survival, apoptosis, gene regulation, and motility. MAPK pathways consist of a relay of consecutive phosphorylation events exerted by MAPK kinase kinases, MAPK kinases, and MAPKs. Conventional MAPKs are characterized by a conserved Thr-X-Tyr motif in the activation loop of the kinase domain, while atypical MAPKs lack this motif and do not seem to be organized into the classical three-tiered kinase cascade. One functional group of conventional and atypical MAPK substrates consists of protein kinases known as MAPK-activated protein kinases. Eleven mammalian MAPK-activated protein kinases have been identified, and they are divided into five subgroups: the ribosomal-S6-kinases RSK1-4, the MAPK-interacting kinases MNK1 and 2, the mitogen- and stress-activated kinases MSK1 and 2, the MAPK-activated protein kinases MK2 and 3, and the MAPK-activated protein kinase MK5 (also referred to as PRAK). MK5/PRAK is the only MAPK-activated protein kinase that is a substrate for both conventional and atypical MAPK, while all other MAPKAPKs are exclusively phosphorylated by conventional MAPKs. This review focuses on the structure, activation, substrates, functions, and possible implications of MK5/PRAK in malignant and nonmalignant diseases.
丝裂原活化蛋白激酶（MAPK）途径是重要的信号转导途径，控制包括增殖、分化、存活、凋亡、基因调控和运动在内的关键细胞过程。MAPK 途径由 MAPK 激酶激酶、MAPK 激酶和 MAPK 连续磷酸化事件的传递组成。传统的 MAPK 特征在于激酶结构域激活环中的保守 Thr-X-Tyr 基序，而非典型的 MAPK 缺乏此基序，似乎不组织成经典的三级激酶级联。传统和非典型 MAPK 的一个功能组底物由称为 MAPK 激活蛋白激酶的蛋白激酶组成。已经鉴定出 11 种哺乳动物 MAPK 激活蛋白激酶，它们分为五个亚组：核糖体-S6-激酶 RSK1-4、MAPK 相互作用激酶 MNK1 和 2、有丝分裂原和应激激活激酶 MSK1 和 2、MAPK 激活蛋白激酶 MK2 和 3 以及 MAPK 激活蛋白激酶 MK5（也称为 PRAK）。MK5/PRAK 是唯一受传统和非典型 MAPK 共同作用的 MAPK 激活蛋白激酶，而所有其他 MAPKAPKs 仅被传统 MAPK 磷酸化。这篇综述重点介绍了 MK5/PRAK 的结构、激活、底物、功能以及在恶性和非恶性疾病中的可能意义。
