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

Transforming growth factor-beta (TGF-beta) regulates a variety of cellular activities including cell growth, differentiation and extracellular matrix production. The TGF-beta type I and type II serine/threonine kinase receptors (TbetaRI and TbetaRII) have been identified as signal-transducing TGF-beta receptors. This study was undertaken to examine the role of the type I and type II receptors in TGF-beta-induced extracellular matrix production of lung fibroblasts. We constructed expression plasmids containing truncated derivatives of TbetaRI and TbetaRII that lacked the cytoplasmic serine/threonine kinase domain (TbetaRI deltaK and TbetaRII deltaK), and transfected them into lung fibroblasts. TbetaRII deltaK expressed by lung fibroblasts was able to bind 125I-TGF-beta1, whereas TbetaRI deltaK was unable to bind ligand when expressed alone. Co-expression with TbetaRII was required for binding and cross-linking of TGF-beta1 to TbetaRI deltaK. Lung fibroblasts upregulate tenascin and fibronectin production when treated with TGF-beta1. The kinase-defective deletions of both TbetaRI and TbetaRII were dominant-acting inhibitors of TGF-beta signal transduction. Expression of either TbetaRI deltaK or TbetaRII deltaK alone was sufficient to block TGF-beta-induced tenascin and fibronectin production of lung fibroblasts. The results indicate that both TbetaRI and TbetaRII were required for TGF-beta signaling in regulation of extracellular matrix production by lung fibroblasts.