The integrin alphavbeta3 is a receptor for the latency-associated peptides of transforming growth factors beta1 and beta3

The integrins α_vβ₁, α_vβ₅, α_vβ₆ and α_vβ₈ have all recently been shown to interact with the RGD motif of the latency-associated peptide (LAPβ₁) of transforming growth factor β₁ (TGFβ₁), with binding to α_vβ₆ and α_vβ₈ leading to TGFβ₁ activation. Previously it has been suggested that the remaining α_v integrin, α_vβ_3, does not interact with LAPβ₁. However, here we show clearly that α_vβ₃ does indeed interact with the LAPβ₁ RGD motif. This interaction is similar to other α_vβ₃ ligands in terms of the cations required for adhesion, the concentrations of LAPβ₁ required for binding and the ability of a small-molecule inhibitor of α_vβ₃, SB223245, to block the interaction. Using glutathione S-transferase fusion proteins we have mapped a minimal integrin-binding loop in LAPβ₁ and then used this approach to probe the integrin-binding properties of the equivalent loops in LAPβ₂ and LAPβ₃. We show that the RGD motif of LAPβ₃ also interacts with α_vβ₃, in addition to α_vβ₆, α_vβ₁ and α_vβ₅, whereas the corresponding loop in LAPβ₂ does not interact with these integrins. These observations therefore correct a previously reported inaccuracy in the literature. Furthermore, they are important as they link α_vβ₃ and TGFβ, which may have implications in cancer and a number of inflammatory and fibrotic diseases where expression of both proteins has been documented.