Stromal cell-derived factor-1 (CXCL12) activates integrins by direct binding to an allosteric ligand-binding site (site 2) of integrins without CXCR4.

ABSTRACT: Leukocyte arrest on the endothelial cell surface during leukocyte extravasation is induced by rapid integrin activation by chemokines. We recently reported that fractalkine induces integrin activation without its receptor CX3CR1 through binding to the allosteric site (site 2) of integrins. Peptides from site 2 bound to fractalkine and suppressed integrin activation by fractalkine. We hypothesized that this is not limited to membrane-bound fractalkine. We studied whether stromal cell-derived factor-1 (SDF1), another chemokine that plays a critical role in leukocyte arrest, activates integrins through binding to site 2. We describe here that (1) SDF1 activated soluble integrin αvβ3 in cell-free conditions, suggesting that SDF1 can activate αvβ3 without CXCR4; (2) site 2 peptide bound to SDF1

SUBMITTER: Fujita M 

PROVIDER: S-EPMC7485306 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature