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- W2115809984 abstract "See related article, pages 1269–1279Integrins are α- and β-subunit heterodimeric receptors that mediate divalent cation-dependent cell-cell and cell-matrix adhesion through tightly regulated interactions with ligands central to inflammation, immunity, hemostasis, and tumor metastasis.1 Integrins have been viewed to function within a 2-state model. In response to cell activation signals, integrins switch from a low-affinity to a high-affinity ligand-binding state. These inactive and active integrin conformations have been corroborated structurally.2 In this issue of Circulation Research , Wolf and coworkers3 have mapped a novel interaction site within the ligand-binding I-domain of the αM-subunit. Taken with the synthesis herein, these data provide tantalizing evidence that the 2-state model of integrin activation and deactivation may be oversimplified.Recruitment of circulating leukocytes in inflammation requires multistep adhesive and signaling events mediated, in part, by members of the β2-integrin family, LFA-1 (αLβ2, CD11a/CD18), Mac-1 (αMβ2, CD11b/CD18), p150,95 (αMβ2, CD11c/CD18), and αDβ2 (CD11d/CD18).4 Mac-1 is the most abundant β2-integrin on neutrophils and monocytes and is a highly promiscuous receptor, capable of binding a broad repertoire of ligands (Figure, A) and facilitating key leukocyte functions including migration, coagulation, proteolysis, phagocytosis, oxidative burst, and signaling.5–9 Elegant structural studies by several groups have begun to elucidate the molecular basis for such broad ligand recognition by Mac-1. A subset of integrin α-subunits, including αM of Mac-1, contains an inserted domain (I domain) of ≈200 amino acids that is implicated in ligand binding. The αMI-domain contributes broadly to the recognition of ligands by αMβ …" @default.
- W2115809984 created "2016-06-24" @default.
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- W2115809984 date "2011-11-11" @default.
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- W2115809984 title "Opening the Field of Integrin Biology to “Biased Agonism”" @default.
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- W2115809984 doi "https://doi.org/10.1161/circresaha.111.257980" @default.
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