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-beta), the TGF-beta type II receptor (betaR-II) binds TGF-beta, presents the ligand to type I receptor, and forms a heterodimeric receptor complex that functions as an active signaling receptor. We isolated cDNA clones encoding an isoform of human betaR-II from vascular endothelial cells by RT-PCR. The deduced structure of the isoform designated as betaR-IIb contained a 25-amino-acid residue inserted at the extracellular region. The insert exhibited 73% homology to a similar insertion found in a mouse betaR-II variant. BetaR-IIb mRNA was ubiquitously expressed in all human cell lines examined. BetaR-IIb as well as betaR-II stably expressed in betaR-II deficient DR26 cells acted as a functional receptor transducing signals from TGF-beta for growth inhibition and the transcriptional activation of the plasminogen activator inhibitor-1 promoter. These results indicated that the betaR-IIb expressed in mammalian cells functions indistinguishably from in betaR-II. The potential function of betaR-IIb is discussed.