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-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 (T beta RI and T beta RII) 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 T beta RI and T beta RII that lacked the cytoplasmic serine/threonine kinase domain (T beta RI Delta K and T X RII Delta K), and transfected them into lung fibroblasts. T beta RII Delta K expressed by lung fibroblasts was able to bind I-125-TGF-beta 1, whereas T beta RI Delta K was unable to bind ligand when expressed alone. Go-expression with T beta RII was required for binding and cross-linking of TGF-beta 1 to T beta RI Delta K. Lung fibroblasts upregulate tenascin and fibronectin production when treated with TGF-beta 1 The kinase-defective deletions of both T beta RI and T beta RII were dominant-acting inhibitors of TGF-beta signal transduction. Expression of either T beta RI Delta K or T beta RII Delta K alone was sufficient to block TGF-beta-induced tenascin and fibronectin production of lung fibroblasts. The results indicate that both T beta RI and T beta RII were required for TGF-beta signaling in regulation of extracellular matrix production by lung fibroblasts. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.