Cancer Research UK Edinburgh Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XR, United Kingdom; email:
Annu Rev Cell Dev Biol. 2018 Oct 6;34:29-58. doi: 10.1146/annurev-cellbio-100617-062559. Epub 2018 Aug 15.
Cell adhesion to macromolecules in the microenvironment is essential for the development and maintenance of tissues, and its dysregulation can lead to a range of disease states, including inflammation, fibrosis, and cancer. The biomechanical and biochemical mechanisms that mediate cell adhesion rely on signaling by a range of effector proteins, including kinases and associated scaffolding proteins. The intracellular trafficking of these must be tightly controlled in space and time to enable effective cell adhesion and microenvironmental sensing and to integrate cell adhesion with, and compartmentalize it from, other cellular processes, such as gene transcription, protein degradation, and cell division. Delivery of adhesion receptors and signaling proteins from the plasma membrane to unanticipated subcellular locales is revealing novel biological functions. Here, we review the expected and unexpected trafficking, and sites of activity, of adhesion and growth factor receptors and intracellular kinase partners as we begin to appreciate the complexity and diversity of their spatial regulation.
细胞与微环境中大分子的黏附对于组织的发育和维持至关重要，其失调可导致多种疾病状态，包括炎症、纤维化和癌症。介导细胞黏附的生物力学和生化机制依赖于一系列效应蛋白的信号转导，包括激酶和相关支架蛋白。这些蛋白的细胞内运输必须在时空上受到严格控制，以实现有效的细胞黏附和微环境感应，并将细胞黏附与其他细胞过程（如基因转录、蛋白质降解和细胞分裂）整合和分隔开。黏附受体和信号蛋白从质膜向意想不到的亚细胞区室的运输揭示了新的生物学功能。在这里，我们综述了黏附因子和生长因子受体以及细胞内激酶伴侣的预期和意外的运输和活性部位，因为我们开始理解它们空间调节的复杂性和多样性。
