Transforming growth factor beta (TGF-beta) is a multifunctional factor that regulates many aspects of cellular processes. TGF-beta signals through a heteromeric complex of type-I and type-II receptors, which both belong to the transmembrane (TM) receptor serine/threonine kinase family. Reported here is the isolation of a subtype of the human TGF-beta receptor type II from a cDNA library using a Saccharomyces cerevisiae mutant. This yeast mutant has a defect in the expression of the gene encoding inositol-1-phosphate synthase and requires myo-inositol for its growth. The cloned subtype of the TGF-beta receptor type II has a 25-amino-acid insertion relative to the reported receptor type-II sequence. In addition to that encoding the TGF-beta receptor, two more human genes were obtained using the same yeast mutant. They encode the protein phosphatase type 2A regulatory subunit A and a 14-3-3 protein which is known as a regulatory protein for protein kinases. These results clearly indicate that these human genes function in yeast cells. It is also suggested that yeast possesses a signal transduction mechanism resembling the human TGF-beta-mediated signaling pathway.