Transforming growth factor-βs (TGF-β) are secreted as latent complexes consisting of the TGF-β dimer, the TGF-β propeptide dimer, and the latent TGF-β binding protein (LTBP). Although the bonds between TGF-β and its propeptide are cleaved intracellulary, the propeptide associates with TGF-β by electrostatic interactions, thereby conferring latency to the complex. We reported that a specific sequence of LTBP-1 is required for latent TGF-β activation by the integrin αvβ6. Here we describe a 24 amino acid sequence from the hinge domain required for activation. The LTBP-1 polypeptide rL1N, which includes the hinge, associates with fibronectin in binding assays. We present evidence that fibronectin null cells minimally activate latent TGF-β and poorly incorporate the active hinge sequence into their matrix. In addition, cells missing the fibronectin receptor α5β1 exhibit defective activation of latent TGF-β by αvβ6 and decreased matrix incorporation. The results indicate specificity for integrin-mediated latent TGF-β activation that include unique sequences in LTBP-1 and an appropriate matrix molecule.
All Science Journal Classification (ASJC) codes
- Molecular Biology