Protein tyrosine phosphatases in cell adhesion

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.

LAR Receptor Tyrosine Phosphatase Family in Healthy and Diseased Brain

“…RPTPs were discovered in 1988 ( Tonks et al, 1988 ), and have been increasingly studied because they not only participate in cellular signaling through their phosphatase activity, but also by acting as adhesion molecules often independently of their catalytic domains ( Young et al, 2021 ). Amongst these dual-function molecules, type IIA RPTPs arise as important modulators of several cellular processes within the brain, acting as signaling and adhesion molecules.…”

How integrin phosphorylations regulate cell adhesion and signaling

“…The β 1 -, β 2 -, and β 3 -integrins are best known, and many of the regulatory mechanisms appear similar in the different integrin families. A few protein kinases and phosphatases have been identified to be involved in integrin phosphorylation, but here much additional work is needed [ 27 , 54 ].…”

Targeting Breast Cancer and Their Stem Cell Population through AMPK Activation: Novel Insights

“…PTP1B expression has been shown to promote tumorigenesis in breast cancers, and several in vivo studies have shown that PTP1B knockout results in delayed tumour formation [129,133,134]. Inhibition of PTP1B results in decreased cell adhesion by downregulation of claudin-1, FAK, and E-cadherin and induces anoikis [120,135,136]. Recently, many anticancer agents have targeted for breast cancer in vitro and in vivo and have shown to act via inhibition of PTP1B activity.…”