A panel of 71 chemically mutagenized Mv1Lu mink lung epithelial cell clones were selected based on their resistance to the growth inhibitory action of transforming growth factor β1 (TGF-β1) and TGF-β2. Characterization of TGF-β receptors in these mutants indicates that the TGF-β-binding membrane proteoglycan, betaglycan, is apparently normal in all of them. However, 14 of the mutant clones are defective in TGF-β receptor type I, and 22 clones are simultaneously defective in receptor types I and II. The clones with type I receptor defects fall into two distinct phenotypes, called R and LR. The R phenotype is characterized by the lack of detectable type I receptors, and has been previously described (Boyd, F.T., and Massague, J. (1989) J. Biol. Chem. 264, 2272-2278). LR mutants are characterized by expression of low levels of type I receptor and are, like the R mutants, completely resistant to growth inhibition by TGF-β1 or -β2. Mutant clones that are simultaneously defective in receptor types I and II fall into three distinct phenotypes. These included DRa mutants which are characterized by lack of detectable receptor types I and II, DRb mutants which are characterized by expression of anomalously low levels of receptor types I and II, and DRc mutants which are characterized by low expression of both receptor types and an anomalously fast electrophoretic mobility of the type II receptor protein. All mutants that have a low level of type II receptor are also defective in type I receptor. In addition to the loss of growth inhibitory response, the receptor-defective mutants described here have lost all other responses to TGF-β1 and -β2 known to occur in parental Mv1Lu cells. The defects present in these mutant clones are not encountered in clones isolated from nonmutagenized parental Mv1Lu cells or in mutagenized cells that had not been exposed to selection with TGF-β. The results implicate TGF-β receptor types I and II in the mediation of a common set of cellular responses to TGF-β. Furthermore, the high relative frequency of isolation of DR mutants raises the possibility that receptor types I and II interact as part of a common signaling TGF-β receptor complex.
|Original language||English (US)|
|Number of pages||7|
|Journal||Journal of Biological Chemistry|
|State||Published - 1990|
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology