Integrin αVβ6-mediated activation of latent TGF-β requires the latent TGF-β binding protein-1
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- 7 June 2004
- journal article
- Published by Rockefeller University Press in The Journal of cell biology
- Vol. 165 (5) , 723-734
- https://doi.org/10.1083/jcb.200312172
Abstract
Transforming growth factor-βs (TGF-β) are secreted as inactive complexes containing the TGF-β, the TGF-β propeptide, also called the latency-associated protein (LAP), and the latent TGF-β binding protein (LTBP). Extracellular activation of this complex is a critical but incompletely understood step in TGF-β regulation. We have investigated the role of LTBP in modulating TGF-β generation by the integrin αVβ6. We show that even though αvβ6 recognizes an RGD on LAP, LTBP-1 is required for αVβ6-mediated latent TGF-β activation. The domains of LTBP-1 necessary for activation include the TGF-β propeptide-binding domain and a basic amino acid sequence (hinge domain) with ECM targeting properties. Our results demonstrate an LTBP-1 isoform-specific function in αVβ6-mediated latent TGF-β activation; LTBP-3 is unable to substitute for LTBP-1 in this assay. The results reveal a functional role for LTBP-1 in latent TGF-β activation and suggest that activation of specific latent complexes is regulated by distinct mechanisms that may be determined by the LTBP isoform and its potential interaction with the matrix.Keywords
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