Multiple activation states of VLA-4. Mechanistic differences between adhesion to CS1/fibronectin and to vascular cell adhesion molecule-1.

Mutational Evidence for Control of Cell Adhesion Through Integrin Diffusion/Clustering, Independent of Ligand Binding

“…Ligand binding was carried out in 2 mM manganese, because calcium and magnesium (either alone, or together, at ‫ف‬ 1-2 mM) fail to support binding of soluble VCAM (15,26). To alleviate concern that manganese might mask differences in VCAM binding by inducing high affinity ␣ 4 ␤ 1 (15,26,27), manganese was titrated over a range of concentrations, whereas VCAM was held constant at 4 nM VCAM-Ig-AP (Fig. 2 C), or 500 nM VCAM-(Fig.…”

Energy landscape differences among integrins establish the framework for understanding activation

“…Studies with K562 cells, in which different integrin α-subunits were transfected to pair with the endogenous β 1 subunit, showed marked differences among β 1 integrins in basal expression of LIBS epitopes and induction of these epitopes with Mn 2+ or ligand (Bazzoni et al, 1998). Furthermore, differences in basal activity were found for the same integrin expressed on different cell types; for example, higher LIBS expression on α 4 β 1 was found on Jurkat than Thp1 cells (Masumoto and Hemler, 1993;Yednock et al, 1995;Shu et al, 2002). The mechanistic basis for these differences has been unclear; indeed, an underlying conceptual framework and quantitative methods for understanding differences among integrins and their activity on different cell types have become available only recently.…”

Loss of talin1 in platelets abrogates integrin activation, platelet aggregation, and thrombus formation in vitro and in vivo

“…2 B ). This defect was due to impaired inside-out activation of ␣ IIb ␤ 3 as Mn 2+ , known to exogenously activate ␤ 1 and ␤ 3 integrins ( 22,23 ), induced fi brinogen binding in both control and Tln1 Ϫ / Ϫ platelets ( Fig. 2 B ).…”