Mitogen-activated protein kinases as key players in osmotic stress signaling.
Mitogen-activated protein kinases as key players in osmotic stress signaling.
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DOI：
10.1016/j.bbagen.2016.05.032
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发表时间：
2016-09
期刊：
影响因子：
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通讯作者：
Xiangyu Zhou;I. Naguro;H. Ichijo;Kengo Watanabe
中科院分区：
文献类型：
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作者：
Xiangyu Zhou;I. Naguro;H. Ichijo;Kengo Watanabe
研究背景渗透压是细胞内外渗透压差引起的。由于水的流入或流出，它诱导细胞肿胀或收缩，从而威胁细胞活动。有丝分裂原活化蛋白激酶（MAPK）在渗透胁迫反应的信号通路中起着重要作用，包括调节细胞内无机离子和有机渗透物质的水平。综述范围本综述了细胞渗透胁迫反应以及所涉及的脊椎动物MAPK信号通路的功能和调节。我们还描述了最近的研究结果，关于凋亡信号调节激酶3（ASK 3），MAP 3 K的成员，以证明其调节作用的信号分子以外的MAPKs.Major conclusionsMAPKs被渗透压迅速激活，并有不同的角色，如细胞体积调节，基因表达，细胞存活/死亡。MAPKs的功能和调节具有明显的细胞类型特异性。基于其在渗透胁迫过程中的活性变化及其对WNK 1-SPAK/OSR 1信号通路的调节，推测ASK 3可能在渗透胁迫的敏感机制和与渗透胁迫相关的细胞功能中发挥重要作用。因此，MAPK通路上游调节子的鉴定将提供关于细胞信号转导机制的有价值的线索，这在哺乳动物中仍然是难以捉摸的。阐明体内MAPK的功能也很重要，因为在生理和病理生理条件下的渗透压往往是由细胞内渗透压的变化引起的。这些研究可能有助于建立针对伴随渗透扰动的疾病的治疗策略。
BackgroundOsmotic stress arises from the difference between intracellular and extracellular osmolality. It induces cell swelling or shrinkage as a consequence of water influx or efflux, which threatens cellular activities. Mitogen-activated protein kinases (MAPKs) play central roles in signaling pathways in osmotic stress responses, including the regulation of intracellular levels of inorganic ions and organic osmolytes.Scope of reviewThe present review summarizes the cellular osmotic stress response and the function and regulation of the vertebrate MAPK signaling pathways involved. We also describe recent findings regarding apoptosis signal-regulating kinase 3 (ASK3), a MAP3K member, to demonstrate its regulatory effects on signaling molecules beyond MAPKs.Major conclusionsMAPKs are rapidly activated by osmotic stress and have diverse roles, such as cell volume regulation, gene expression, and cell survival/death. There is significant cell type specificity in the function and regulation of MAPKs. Based on its activity change during osmotic stress and its regulation of the WNK1-SPAK/OSR1 pathway, ASK3 is expected to play important roles in osmosensing mechanisms and cellular functions related to osmoregulation.General significanceMAPKs are essential for various cellular responses to osmotic stress; thus, the identification of the upstream regulators of MAPK pathways will provide valuable clues regarding the cellular osmosensing mechanism, which remains elusive in mammals. The elucidation ofin vivoMAPK functions is also important because osmotic stress in physiological and pathophysiological conditions often results from changes in the intracellular osmolality. These studies potentially contribute to the establishment of therapeutic strategies against diseases that accompany osmotic perturbation.