A HUMAN TRANSFORMING GROWTH-FACTOR-BETA TYPE-II RECEPTOR THAT CONTAINS AN INSERTION IN THE EXTRACELLULAR DOMAIN

In the signal transduction of transforming growth factor-beta (TGF-bet a), the TGF-beta type II receptor (beta R-II) binds TGF-beta, presents the ligand to type I receptor, and forms a heterodimeric receptor com plex that functions as an active signaling receptor. We isolated cDNA clones encoding an isoform of human beta R-II from vascular endothelia l cells by RT-PCR. The deduced structure of the isoform designated as beta R-IIb contained a 25-amino acid residue inserted at the extracell ular region. The insert exhibited 73% homology to a similar insertion found in a mouse beta R-II variant. beta R-IIb mRNA was ubiquitously e xpressed in all human cell lines examined. beta R-IIb as well as beta R-II stably expressed in beta RII-deficient DR26 cells acted as a func tional receptor transducing signals from TGF-beta for growth inhibitio n and the transcriptional activation of the plasminogen activator inhi bitor-1 promoter. These results indicated that the beta R-IIb expresse d in mammalian cells functions indistinguishably from beta R-II. The p otential function of beta R-IIb is discussed. (C) 1996 Academic Press, Inc.