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• W1527838044 endingPage "193" @default.
• W1527838044 startingPage "157" @default.
• W1527838044 abstract "The arrest of rolling leukocytes at target vascular sites depends on rapid activation of their vascular integrins at endothelial contacts enriched with specific Ig superfamily (IgSF) ligands. Accumulating data suggest that these integrins acquire high affinity to these endothelial ligands in a process tightly regulated by a variety of cytoskeletal conformational changes in their α- and β-subunits. These alterations are controlled by inside-out signals that are induced primarily by chemokines displayed on the endothelium and transduced by G protein-coupled receptors (GPCRs) on the responding leukocytes. The GPCR signals can propagate within milliseconds at submicron ranges. Upon binding their ligands, GPCR-stimulated integrins also undergo outside-in conformational activation, which is accelerated by applied forces. The integrin activator, talin—a universal cytoskeletal adaptor in integrinmediated focal adhesions—plays an instrumental role in this bidirectional activation process, which is critical for leukocyte arrest on endothelial IgSF ligands. Multiple effectors in the immediate vicinity to integrin–talin complexes can determine the extent to which talin may translate a given chemokine signal into a fully productive integrin activation. Substantial heterogeneity exists in the pathways used by different cell types to translate a given combination of chemokines and integrin ligands into leukocyte arrest and subsequent adhesion strengthening on various target endothelia. This chapter highlights the main molecular players in the earliest events of chemokine signaling to lymphocyte integrins and proposes modalities used by rapid chemokine signals to trigger cytoskeletal rearrangements in integrin tails, leading to rapid integrin activation and leukocyte arrest on vascular endothelium." @default.
• W1527838044 created "2016-06-24" @default.
• W1527838044 creator A5002080116 @default.
• W1527838044 date "2009-01-01" @default.
• W1527838044 modified "2023-09-27" @default.
• W1527838044 title "Chapter 6 Membrane–Cytoskeletal Platforms for Rapid Chemokine Signaling to Integrins" @default.
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