title: Ligand-dependent activation of integrin alpha vbeta 3.
abstract: The ability of leukocytes to self-regulate adhesion during transendothelial and extravascular migration is fundamental to the performance of immune surveillance in complex extracellular matrices. Leukocyte adhesion is regulated through the modulation of integrin receptors such as alpha(v)beta(3). In this study, we examined the activation of alpha(v)beta(3) resulting from attachment to vitronectin or fibronectin. In K562 cells stably expressing transfected alpha(v)beta(3), adhesion to vitronectin required tyrosine phosphorylation of the beta(3) subunit and activation of phosphoinositide 3-kinase and protein kinase C. In contrast, adhesion to fibronectin proceeded without beta(3)-tyrosine phosphorylation or the activities of phosphoinositide 3-kinase or protein kinase C. Firm adhesion to both ligands and actin stress fiber formation required both Syk and Rho activity, suggesting that each ligand employs unique signaling pathways to achieve an active integrin complex, likely merging at a common RhoGEF such as Vav. Distinct signaling by a single integrin species interacting with different ligands permits initiation of additional cellular processes specific to the current task and provides an explanation for what has been described as promiscuous ligand specificity among integrins.
authors.affiliation: Department of Cell and Developmental Biology, State University of New York Upstate Medical University, Syracuse, New York 13210, USA.
authors.forename: Boyd
authors.initials: B
authors.lastname: Butler
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Williams
authors.forename: Scott D
authors.initials: SD
authors.lastname: Blystone
mesh_terms: D002448:Cell Adhesion; D005109:Extracellular Matrix / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D020014:K562 Cells; D008024:Ligands; D019096:Vitronectin / Q000378:metabolism*
chemical_list: D005353:Fibronectins; D039302:Integrin alphaVbeta3; D008024:Ligands; D019096:Vitronectin