Transforming growth factor-β (TGF-β) type I and type II receptors are both required for TGF-β-mediated extracellular matrix production in lung fibroblasts

Transforming growth factor-β (TGF-β) regulates a variety of cellular activities including cell growth, differentiation and extracellular matrix production. The TGF-β type I and type II serine/threonine kinase receptors (TβRI and TβRII) have been identified as signal-transducing TGF-β receptors. This study was undertaken to examine the role of the type I and type II receptors in TGF-β-induced extracellular matrix production of lung fibroblasts. We constructed expression plasmids containing truncated derivatives of TβRI and TβRII that lacked the cytoplasmic serine/threonine kinase domain (TβRIΔK and TβRIIΔK), and transfected them into lung fibroblasts. TβRIIΔK expressed by lung fibroblasts was able to bind 125 I-TGF-β1, whereas TβRIΔK was unable to bind ligand when expressed alone. Co-expression with TβRII was required for binding and cross-linking of TGF-β1 to TβRIΔK. Lung fibroblasts upregulate tenascin and fibronectin production when treated with TGF-β1. The kinase-defective deletions of both TβRI and TβRII were dominant-acting inhibitors of TGF-β signal transduction. Expression of either TβRIΔK or TβRIIΔK alone was sufficient to block TGF-β-induced tenascin and fibronectin production of lung fibroblasts. The results indicate that both TβRI and TβRII were required for TGF-β signaling in regulation of extracellular matrix production by lung fibroblasts.