| Abstrakt: |
The integrins αvβ1, αvβ5, αvβ6 and αvβ8 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 αvβ6 and αvβ8 leading to TGFβ1 activation. Previously it has been suggested that the remaining αv integrin, αvβ3, does not interact with LAPβ1. However, here we show clearly that αvβ3 does indeed interact with the LAPβ1 RGD motif. This interaction is similar to other αvβ3 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 αvβ3, 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 αvβ3, in addition to αvβ6, αvβ1 and αvβ5, 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 αvβ3 and TGFβ, which may have implications in cancer and a number of inflammatory and fibrotic diseases where expression of both proteins has been documented. |
