Mutlak Michael, Kehat Izhak
The Rappaport Institute and the Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa 31096, Israel; Department of Cardiology and the Clinical Research Institute at Rambam, Rambam Medical Center, Haifa 31096, Israel.
The Rappaport Institute and the Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa 31096, Israel; Department of Cardiology and the Clinical Research Institute at Rambam, Rambam Medical Center, Haifa 31096, Israel.
Cell Signal. 2021 Aug;84:110033. doi: 10.1016/j.cellsig.2021.110033. Epub 2021 Apr 29.
Pressure overload and other stress stimuli elicit a host of adaptive and maladaptive signaling cascades that eventually lead to cardiac hypertrophy and heart failure. Among those, the mitogen-activated protein kinase (MAPK) signaling pathway has been shown to play a prominent role. The dual specificity phosphatases (DUSPs), also known as MAPK specific phosphatases (MKPs), that can dephosphorylate the MAPKs and inactivate them are gaining increasing attention as potential drug targets. Here we try to review recent advancements in understanding the roles of the different DUSPs, and the pathways that they regulate in cardiac remodeling. We focus on the regulation of three main MAPK branches - the p38 kinases, the c-Jun-N-terminal kinases (JNKs) and the extracellular signal-regulated kinases (ERK) by various DUSPs and try to examine their roles.
压力超负荷和其他应激刺激引发一系列适应性和适应性不良的信号级联反应，最终导致心脏肥大和心力衰竭。其中，丝裂原活化蛋白激酶（MAPK）信号通路已被证明发挥着重要作用。双特异性磷酸酶（DUSPs），也称为MAPK特异性磷酸酶（MKPs），能够使MAPKs去磷酸化并使其失活，作为潜在的药物靶点正受到越来越多的关注。在此，我们试图综述在理解不同DUSPs的作用以及它们在心脏重塑中调节的信号通路方面的最新进展。我们重点关注各种DUSPs对三个主要MAPK分支——p38激酶、c-Jun氨基末端激酶（JNKs）和细胞外信号调节激酶（ERK）的调节，并试图研究它们的作用。
