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细胞黏附中的蛋白酪氨酸磷酸酶。

Protein tyrosine phosphatases in cell adhesion.

机构信息

Signalling Programme, Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, U.K.

Bioinformatics, Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, U.K.

出版信息

Biochem J. 2021 Mar 12;478(5):1061-1083. doi: 10.1042/BCJ20200511.

Abstract

Adhesive structures between cells and with the surrounding matrix are essential for the development of multicellular organisms. In addition to providing mechanical integrity, they are key signalling centres providing feedback on the extracellular environment to the cell interior, and vice versa. During development, mitosis and repair, cell adhesions must undergo extensive remodelling. Post-translational modifications of proteins within these complexes serve as switches for activity. Tyrosine phosphorylation is an important modification in cell adhesion that is dynamically regulated by the protein tyrosine phosphatases (PTPs) and protein tyrosine kinases. Several PTPs are implicated in the assembly and maintenance of cell adhesions, however, their signalling functions remain poorly defined. The PTPs can act by directly dephosphorylating adhesive complex components or function as scaffolds. In this review, we will focus on human PTPs and discuss their individual roles in major adhesion complexes, as well as Hippo signalling. We have collated PTP interactome and cell adhesome datasets, which reveal extensive connections between PTPs and cell adhesions that are relatively unexplored. Finally, we reflect on the dysregulation of PTPs and cell adhesions in disease.

摘要

细胞与周围基质之间的黏附结构对于多细胞生物的发育至关重要。除了提供机械完整性外,它们还是关键的信号中心,能够将细胞外环境的反馈传递到细胞内部,反之亦然。在发育、有丝分裂和修复过程中,细胞黏附必须进行广泛的重塑。这些复合物中的蛋白质的翻译后修饰是活性的开关。酪氨酸磷酸化是细胞黏附中一种重要的修饰,其活性受到蛋白质酪氨酸磷酸酶(PTPs)和蛋白质酪氨酸激酶的动态调控。几种 PTPs 参与了细胞黏附的组装和维持,但它们的信号功能仍未得到明确界定。PTP 可以通过直接去磷酸化黏附复合物的成分或作为支架发挥作用。在这篇综述中,我们将重点介绍人类 PTP,并讨论它们在主要黏附复合物以及 Hippo 信号通路中的作用。我们已经整理了 PTP 相互作用组和细胞黏附组数据集,这些数据集揭示了 PTPs 与细胞黏附之间存在广泛的联系,而这些联系在很大程度上尚未得到探索。最后,我们反思了 PTP 和细胞黏附失调与疾病的关系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d97/7959691/69d67f5ab4eb/BCJ-478-1061-g0001.jpg

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