[SER(77)] TRANSFORMING GROWTH-FACTOR-BETA-1 - SELECTIVE BIOLOGICAL-ACTIVITY AND RECEPTOR-BINDING IN MINK LUNG EPITHELIAL-CELLS

Transforming growth factor-beta 1 (TGF-beta 1) is a homodimeric protei n stabilized by a single disulfide bridge between Cys(77) on the respe ctive monomers and two paired complementary hydrophobic interfaces bet ween the two subunits. A TGF-beta 1 mutant with Cys(77) replaced by se rine has been expressed in stably transfected Chinese hamster ovary ce lls and purified to homogeneity. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis confirms that the sole interchain disulfide bond in TGF-beta 1 has been eliminated. It is 20% as potent as native TGF-b eta 1 in the induction of plasminogen activator inhibitor-1 promoter e xpression in mink lung epithelial cells (Mv1Lu), although it is less t han 1% as potent as native TGF-beta 1 in inhibition of growth in the s ame cell line. The mutant acts as a full agonist in both bioassays. [S er(77)]TGF-beta 1 binds to soluble type II receptors and competes with native TGF-beta 1 in sandwich-enzyme-linked immunosorbent assays; how ever, in Mv1Lu cells, the mutant shows preferential cross-linking to t ype I rather than type II receptors. [Ser(77)]TGF-beta 1 is a useful t ool for understanding the different ligand-receptor complexes and nume rous biological activities of this multifunctional cytokine.