Transforming growth factor-beta inhibition of epithelial cell proliferation linked to the expression of a 53-kDa membrane receptor.
Cells whose proliferation is blocked by transforming growth factor-beta (TGF-beta) express three distinct surface glycoproteins of 53, 73, and 300 kDa that bind TGF-beta with high affinity, but whose function is unknown. We have isolated two classes of chemically-induced Mv1Lu epithelial cell mutants resistant to growth inhibition by TGF-beta. Class R mutants have selectively lost expression of the 53-kDa (type I) TGF-beta-binding protein. They have also lost the ability to respond to TGF-beta with elevated fibronectin expression and cell flattening. Class S mutants bind normally but do not respond to TGF-beta. TGF-beta-resistant mutants retain a contact inhibited, nontransformed phenotype. The properties of S mutants suggest that they are defective in the TGF-beta signal transduction mechanism, while the results with R mutants identify the type I TGF-beta-binding protein as the receptor involved in mediating TGF-beta actions on cell adhesion and proliferation.
Boyd
F T
FT
Department of Biochemistry, University of Massachusetts Medical School, Worcester 01655.
Massagué
J
J
D000818:Animals; D002448:Cell Adhesion; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D004261:DNA Replication / Q000187:drug effects; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D005353:Fibronectins / Q000096:biosynthesis; D009154:Mutation; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000235:genetics; D018125:Receptors, Transforming Growth Factor beta; D015291:Transforming Growth Factors / Q000378:metabolism / Q000494:pharmacology*
D005353:Fibronectins; D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta; D015291:Transforming Growth Factors