Characterization of the three mammalian transforming growth factor-β (TGF-β) isoforms, TGF-β1, -β2, and -β3, indicates that TGF-β3 is somewhat more potent (ED50 = 0.5 pM versus 2 pM) than TGF-β1 and TGF-β2 as a growth inhibitor of the Mv1Lu mink lung epithelial cell line. In the fetal bovine heart endothelial (FBHE) cell line, however, TGF-β1 and -β3 are at least 50-fold more potent than TGF-β2 which is a very weak growth inhibitor (ED50 ≥ 0.5 nM). Thus, as growth inhibitors, TGF-β1 and -β3 resemble each other more than TGF-β2. The presence of serum α2-macroglobulin in the FBHE cell assays decreases the biological potency of TGF-βS, in particular TGF-β2. This effect of α2-macroglobulin, however, is not sufficient to explain the low responsiveness of FBHE cells to TGF-β2. Evaluation of the role of TGF-β receptors as determinants of cell-specific responsiveness to TGF-β isoforms indicates that TGF-β1, -β2, and -β3 have similar affinity for the membrane proteoglycan, betaglycan. They differ, however, in their ability to bind to receptor types I and II which are implicated in TGF-β signal transduction. TGF-β1 is similar, albeit not identical, to TGF-β3 and much more potent than TGF-β2 as a competitor for binding to the overall population of receptors I and II in all cell lines tested. A subset of receptors I and II has been identified in Mv1Lu cells which has high affinity for TGF-β2 (KD ∼ 10 pM) and binds this factor at concentrations that are biologically active in Mv1Lu cells. This receptor subset could not be detected in FBHE cells, suggesting that cell-specific differences in the level of high affinity TGF-β2 receptors may lead to cell-specific differences in responsiveness to this isoform. Thus, despite their structural and biological similarities, TGF-β1, -β2, and -β3 diverge in their ability to bind to receptors in a manner that correlates with their potency as growth inhibitors.
|Original language||English (US)|
|Number of pages||6|
|Journal||Journal of Biological Chemistry|
|State||Published - Nov 25 1990|
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology