Cloning and genomic organization of the human transforming growth factor-beta type I receptor gene.

Transforming growth factor-beta (TGF beta) regulates cell cycle progression by a unique signaling mechanism that involves its binding to the type II (T beta R-II) TGF beta receptor and activation of type I (T beta R-I). Both are transmembrane serine-threonine receptor kinases. As various types of human tumor cells are often refractory to TGF beta-mediated cell cycle arrest, it is likely that the T beta R-I receptor is inactivated in many of these cases. We determined the intron-exon organization of the TGFBR1 gene. We report here that this gene is approximately 31 kb in length and consists of nine exons. The organization of the segment of the TGFBR1 gene that encodes the C-terminal portion of the serine-threonine kinase domain appears to be highly conserved between members of the R-I gene family. This information should facilitate and expedite the structural analysis of TGFBR1 in human tumors and possibly other disease states.