Anti-Kindlin 2 Antibody [3A3] (A277536)

Extensive studies have shown that talin is the essential player for inside-out activation of integrins by binding to the intracellular tail of ß integrins. Here we show that, while talin binding is essential for inside-out integrin activation in focal adhesions, it is dispensable in curved adhesions - a distinct adhesion architecture exclusively mediated by integrin avß5 and selectively formed at curved membranes. Instead, a curvature-sensing protein FCHo2 binds to the HDRRE motif in integrin ß5's cytoplasmic tail and inside-out activates integrin avß5 in curved adhesions. FCHo2 does not bind to a similar motif in the homologous integrin ß3. We identify a pivotal tryptophan (W), which is conserved in all homologous ß integrins except ß5, where it is replaced by a tyrosine (Y766). This tyrosine substitution is crucial for integrin ß5's unique capability in forming curved adhesions. Furthermore, our studies suggest that the phosphorylation state of Y766 regulates whether integrin ?vß5 forms curved adhesions or focal adhesions. Overall, our work unveils distinct molecular interactions and regulatory mechanisms between curved adhesions and focal adhesions.