Integrated Science Center, Department of Biology, College of William and Mary, Williamsburg, VA 23185, USA.
Int J Mol Sci. 2021 Nov 22;22(22):12595. doi: 10.3390/ijms222212595.
Mitogen-activated protein kinase (MAPK) signaling pathways are highly conserved regulators of eukaryotic cell function. These enzymes regulate many biological processes, including the cell cycle, apoptosis, differentiation, protein biosynthesis, and oncogenesis; therefore, tight control of the activity of MAPK is critical. Kinases and phosphatases are well established as MAPK activators and inhibitors, respectively. Kinases phosphorylate MAPKs, initiating and controlling the amplitude of the activation. In contrast, MAPK phosphatases (MKPs) dephosphorylate MAPKs, downregulating and controlling the duration of the signal. In addition, within the past decade, pseudoenzymes of these two families, pseudokinases and pseudophosphatases, have emerged as bona fide signaling regulators. This review discusses the role of pseudophosphatases in MAPK signaling, highlighting the function of phosphoserine/threonine/tyrosine-interacting protein (STYX) and TAK1-binding protein (TAB 1) in regulating MAPKs. Finally, a new paradigm is considered for this well-studied cellular pathway, and signal transduction pathways in general.
丝裂原活化蛋白激酶（MAPK）信号通路是真核细胞功能高度保守的调节者。这些酶调节许多生物过程，包括细胞周期、细胞凋亡、分化、蛋白质生物合成和致癌作用；因此，MAPK 活性的严格控制至关重要。激酶和磷酸酶分别被认为是 MAPK 的激活剂和抑制剂。激酶磷酸化 MAPK，启动并控制激活的幅度。相比之下，MAPK 磷酸酶（MKP）去磷酸化 MAPK，下调并控制信号的持续时间。此外，在过去十年中，这两个家族的伪酶，即假激酶和假磷酸酶，已成为真正的信号调节因子。本综述讨论了伪磷酸酶在 MAPK 信号中的作用，重点介绍了磷酸丝氨酸/苏氨酸/酪氨酸相互作用蛋白（STYX）和 TAK1 结合蛋白（TAB1）在调节 MAPK 中的功能。最后，考虑了这一研究充分的细胞途径以及一般的信号转导途径的新范例。
