New Insights into Integrins

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Biological Factors".

Deadline for manuscript submissions: 31 October 2024 | Viewed by 461

Special Issue Editor


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Guest Editor
Department of Dermatology, School of Medicine, University of California–Davis, 4645 Second Ave., Research III Suite 3300, Sacramento, CA 95817, USA
Interests: integrin-growth factor crosstalk; regulation of integrin activation; identification of new integrin ligands
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Special Issue Information

Dear Colleagues,

Integrins were originally identified as a family of receptors for extracellular molecules (e.g., fibronectin) and cell surface molecules (e.g., ICAM-1) in the 1980s. Since, it has been discovered that integrins also interact with soluble ligands such as growth factors (e.g., FGF-1, IGF-1), and almost a decade ago, that several growth factors bind to integrins and cognate receptors simultaneously and generate an integrin–growth factor–cognate receptor ternary complex (ternary complex model). Moreover, growth factor mutants defective in integrin binding are defective in signaling and act as antagonists. It has been recently shown that the a6b1–FGF2–FGFR ternary complex plays a critical role in stem cell maintenance. Additionally, we identified an allosteric site of integrins (site 2) which is distinct from the classical RGD-binding site. Several integrin ligands (e.g., inflammatory chemokines and inflammatory proteins such as secreted PLA2-IIA) bind and induce integrin activation in an allosteric manner. Site 2 was shown to be a binding site for an inflammatory lipid mediator (25-hydroxycholesterol) and is involved in inflammatory signaling in innate immunity. The integrin–growth factor interaction and allosteric activation through site 2 should pave the path to new therapeutic targets. Thus, this Special Issue is designed to facilitate the progress of newly opened fields of integrin study.

Prof. Dr. Yoshikazu Takada
Guest Editor

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Keywords

  • integrins
  • growth factors
  • ligands

Published Papers (1 paper)

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Research

18 pages, 3609 KiB  
Article
FGF1 Suppresses Allosteric Activation of β3 Integrins by FGF2: A Potential Mechanism of Anti-Inflammatory and Anti-Thrombotic Action of FGF1
by Yoko K. Takada, Xuesong Wu, David Wei, Samuel Hwang and Yoshikazu Takada
Biomolecules 2024, 14(8), 888; https://doi.org/10.3390/biom14080888 - 23 Jul 2024
Viewed by 305
Abstract
Several inflammatory cytokines bind to the allosteric site (site 2) and allosterically activate integrins. Site 2 is also a binding site for 25-hydroxycholesterol, an inflammatory lipid mediator, and is involved in inflammatory signaling (e.g., TNF and IL-6 secretion) in addition to integrin activation. [...] Read more.
Several inflammatory cytokines bind to the allosteric site (site 2) and allosterically activate integrins. Site 2 is also a binding site for 25-hydroxycholesterol, an inflammatory lipid mediator, and is involved in inflammatory signaling (e.g., TNF and IL-6 secretion) in addition to integrin activation. FGF2 is pro-inflammatory and pro-thrombotic, and FGF1, homologous to FGF2, has anti-inflammatory and anti-thrombotic actions, but the mechanism of these actions is unknown. We hypothesized that FGF2 and FGF1 bind to site 2 of integrins and regulate inflammatory signaling. Here, we describe that FGF2 is bound to site 2 and allosterically activated β3 integrins, suggesting that the pro-inflammatory action of FGF2 is mediated by binding to site 2. In contrast, FGF1 bound to site 2 but did not activate these integrins and instead suppressed integrin activation induced by FGF2, indicating that FGF1 acts as an antagonist of site 2 and that the anti-inflammatory action of FGF1 is mediated by blocking site 2. A non-mitogenic FGF1 mutant (R50E), which is defective in binding to site 1 of αvβ3, suppressed β3 integrin activation by FGF2 as effectively as WT FGF1. Full article
(This article belongs to the Special Issue New Insights into Integrins)
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