Transforming growth factor-β (TGF-β) is secreted in a latent form and activated during co-culture of endothelial cells and smooth muscle cells. Plasmin located on the surface of endothelial cells is required for the activation of latent TGF-β (LTGF-β) during co-culture, and the targeting of LTGF-β to the cellular surface is requisite for its activation. In the present study, the cellular targeting of LTGF-β was examined. We detected the specific binding of 125I-large LTGF-β1 isolated from human platelets to smooth muscle cells but not to endothelial cells. A mAb against the latency-associated peptide (LAP) of large LTGF-β1 complex, which blocked the binding of 125I-large LTGF-β1 to smooth muscle cells, inhibited the activation of LTGF-β during co-culture. The binding of 125I-large LTGF- β1 could not be competed either by mannose-6-phosphate (300 μM) or by the synthetic peptide Arg-Gly-Asp-Ser (300 μg/ml). These results indicate that the targeting of LTGF-β to smooth muscle cells is required for the activation of LTGF-β during co-culture of endothelial cells and smooth muscle cells. The targeting of LTGF-β to smooth muscle cells is mediated by LAP, and the domain of LAP responsible for the targeting to smooth muscle cells may not be related to mannose-6-phosphate or an Arg-Gly-Asp sequence, both of which have been previously proposed as candidates for the cellular binding domains within LAP.
ASJC Scopus subject areas
- Cell Biology