Svec Kathryn V, Howe Alan K
Department of Pharmacology, University of Vermont, Burlington, VT, United States.
Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, V T, United States.
Front Mol Biosci. 2022 Jul 22;9:953093. doi: 10.3389/fmolb.2022.953093. eCollection 2022.
Cell migration requires establishment and maintenance of directional polarity, which in turn requires spatial heterogeneity in the regulation of protrusion, retraction, and adhesion. Thus, the signaling proteins that regulate these various structural processes must also be distinctly regulated in subcellular space. Protein Kinase A (PKA) is a ubiquitous serine/threonine kinase involved in innumerable cellular processes. In the context of cell migration, it has a paradoxical role in that global inhibition or activation of PKA inhibits migration. It follows, then, that the subcellular regulation of PKA is key to bringing its proper permissive and restrictive functions to the correct parts of the cell. Proper subcellular regulation of PKA controls not only when and where it is active but also specifies the targets for that activity, allowing the cell to use a single, promiscuous kinase to exert distinct functions within different subcellular niches to facilitate cell movement. In this way, understanding PKA signaling in migration is a study in context and in the elegant coordination of distinct functions of a single protein in a complex cellular process.
细胞迁移需要建立和维持方向性极性，而这又需要在突出、回缩和黏附的调节中存在空间异质性。因此，调节这些不同结构过程的信号蛋白也必须在亚细胞空间中受到不同的调节。蛋白激酶A（PKA）是一种普遍存在的丝氨酸/苏氨酸激酶，参与无数细胞过程。在细胞迁移的背景下，它具有矛盾的作用，即PKA的整体抑制或激活都会抑制迁移。那么，PKA的亚细胞调节是将其适当的允许和限制功能带到细胞正确部位的关键。PKA的适当亚细胞调节不仅控制其何时何地活跃，还指定该活性的靶点，使细胞能够使用单一的、杂乱的激酶在不同的亚细胞微环境中发挥不同的功能，以促进细胞运动。通过这种方式，理解迁移中的PKA信号传导是一项关于在复杂细胞过程中对单一蛋白质不同功能进行背景和精确协调的研究。
