New Insights into Integrins

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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• integrins
• growth factors
• ligands