Abstract
Inadequate function of Transforming Growth Factor- (TGF-) β is involved in numerous disease states including immune disorders and cancer, rendering this polypeptide and its receptor an attractive target for pharmaceutical interference. We have developed a novel microscale functional test system suited for the investigation of ligand-induced receptor activation and the automatable evaluation of potential agonists and antagonists. Hybrid receptors were constructed from the cytoplasmic domain of the human interleukin-4 (IL-4) receptor α-chain and extracellular domains of a TGF-β type I and type II receptor, respectively. These chimeras were stably introduced into the factor-dependent murine cell line Ba/F3 along with an IL-4-inducible luciferase reporter gene construct, yielding a reporter cell line which responds to productive ligand?receptor interactions by specific luciferase activity in a dose-dependent fashion. A model experiment employing inhibitory peptides demonstrates that the devised reporter cell provides a rational readout for TGF-β activity on target cells and its impairment by specific antagonists.
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