How integrin phosphorylations regulate cell adhesion and signaling

Abstract

Cell adhesion is essential for the formation of organs, cellular migration, and interaction with target cells and the extracellular matrix. Integrins are large protein α/β-chain heterodimers and form a major family of cell adhesion molecules. Recent research has dramatically increased our knowledge of how integrin phosphorylations regulate integrin activity. Phosphorylations determine the signaling complexes formed on the cytoplasmic tails, regulating downstream signaling. α-Chain phosphorylation is necessary for inducing β-chain phosphorylation in LFA-1, and the crosstalk from one integrin to another activating or inactivating its function is in part mediated by phosphorylation of β-chains. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus receptor angiotensin-converting enzyme 2 (ACE2) and possible integrin coreceptors may crosstalk and induce a phosphorylation switch and autophagy.

Proteomics and Phosphoproteomics of Circulating Extracellular Vesicles Provide New Insights into Diabetes Pathobiology

“…We speculate that the apparent integrin switch is potentially triggered by the phosphorylation events occurring on those three integrins. In support of our reasoning, the crosstalk between integrins conducing to the activation or inactivation of its function is mediated, at least in part, by phosphorylation of the β-chains, and phosphorylation switches may induce the crosstalk between integrins and other receptors [ 68 ]. However, our evidence is only correlative; therefore, we cannot determine causality.…”

Adhesion of Dictyostelium Amoebae to Surfaces: A Brief History of Attachments

“…The phosphorylation of functional motifs in the cytoplasmic integrin tails leads to conformational changes that enable the recruitment of downstream proteins such as 14-3-3, talin, and kindlin ( Gahmberg and Grönholm, 2022 ). Most integrin β-tails contain conserved NPXY motifs that belong to a recognition sequence for phosphotyrosine-binding (PTB) domains ( Calderwood et al, 2003 ).…”

“…Most integrin β-tails contain conserved NPXY motifs that belong to a recognition sequence for phosphotyrosine-binding (PTB) domains ( Calderwood et al, 2003 ). Besides PTBs, Src homology 2 (SH2) domains also bind phosphorylated tyrosine and are important in integrin signaling ( Gahmberg and Grönholm, 2022 ). Instead by canonical tyrosine kinases, tyrosine phosphorylation in Dictyostelium is mediated by tyrosine kinase-like (TLK) proteins ( Goldberg et al, 2006 ).…”

Electrical charge on ferroelectric nanocomposite membranes enhances SHED neural differentiation

“…Paxillin is a cytoskeletal protein involved in actin-membrane attachment at the extracellular matrix site, which plays an important role in the integrin signaling transduction [ 41 ]. Integrin-mediated reorganization of the cytoskeleton requires the phosphorylation of Paxillin tyrosine residues [ 42 ]. As seen in Fig.…”