GH3 pituitary tumor cells contain heteromeric type I and type II receptor complexes for transforming growth factor...

Transforming growth factors beta (TGF-beta s) and activins induce and inhibins block secretion of follicle-stimulating hormone by rat GH3 pituitary tumor cells. Cheifetz et al. (Cheifetz, S., Ling, N., Guillemin, R., and Massagué, J. (1988) J. Biol. Chem. 263, 17225-17228) reported that GH3 cells express a approximately 50-kDa surface protein, termed the type IV TGF-beta receptor, that directly binds all of these peptide hormones. Here we show that GH3 cells express the previously identified type I and type II receptors for TGF-beta and activin-A. Immunoprecipitation of affinity-labeled surface binding proteins with antisera specific to known receptors demonstrated independent heteromeric complexes of TGF-beta types I and II receptors and of activin types I and II receptors. As judged by ligand-binding and cross-linking analysis, TGF-beta binding to the TGF-beta receptors is not inhibited by activin-A and activin-A binding to its receptors is not inhibited by TGF-beta. Screening of a cDNA library from GH3 cells for potential receptor serine-threonine kinases yielded the known types I and II TGF-beta and activin receptors. The presumed common intracellular signaling pathway for TGF-beta and activin in GH3 cells appears to be mediated by distinct cell-surface receptors.