GH3 PITUITARY-TUMOR CELLS CONTAIN HETEROMERIC TYPE-I AND TYPE-II RECEPTOR COMPLEXES FOR TRANSFORMING GROWTH-FACTOR-BETA AND ACTIVIN-A

Transforming growth factors beta (TGF-beta s) and activins induce and inhibins block secretion of follicle-stimulating hormone by rat GH3 pi tuitary tumor cells. Cheifetz et al. (Cheifetz, S., Ling, N., Guillemi n, R., and Massague, J. (1988) J. Biol. Chem. 263, 17225-17228) report ed that GH3 cells express a similar to 50-kDa surface protein, termed the type IV TGF-beta receptor, that directly binds all of these peptid e hormones. Here we show that GH3 cells express the previously identif ied type I and type II receptors for TGF-beta and activin-A. Immunopre cipitation of affinity-labeled surface binding proteins with antisera specific to known receptors demonstrated independent heteromeric compl exes of TGF-beta types I and II receptors and of activin types I and I I receptors. As judged by ligand-binding and cross linking analysis, T GF-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 ser ine-threonine kinases yielded the known types I and II TGF-beta and ac tivin receptors. The presumed common intracellular signaling pathway f or TGF-beta and activin in GH3 cells appears to be mediated by distinc t cell-surface receptors.