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.
Highlights
IntroductionCell adhesions are an essential feature of multicellular life and function as both mechanical links between cells and their environment and as major signalling hubs
Cell adhesion complexes and tyrosine phosphorylationCell adhesions are an essential feature of multicellular life and function as both mechanical links between cells and their environment and as major signalling hubs
The recent explosion of proteomics datasets has enabled us to visualise the extensive connections between protein tyrosine kinases and phosphatases (PTPs), core adhesive complexes and signalling pathways
Summary
Cell adhesions are an essential feature of multicellular life and function as both mechanical links between cells and their environment and as major signalling hubs. In addition to maintaining tissue integrity, adhesion complexes must rapidly remodel to accommodate growth, renewal and repair. Reversible protein tyrosine phosphorylation, which expands the static proteome, allows dynamic changes to protein function that can facilitate such remodelling. The coordinated actions of protein tyrosine kinases and phosphatases (PTPs) control phosphotyrosine levels with high spatiotemporal specificity and are both key players in the regulation of cell adhesions. The repertoire of kinases and PTPs has expanded in concert with increased organismal complexity, reflecting a need for greater regulation and specificity [1]. We will focus on the PTPs and their impact on key adhesive complexes present in human epithelial and endothelial cells
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