Responsiveness to transforming growth factor-beta (TGF-beta) restored by genetic complementation between cells defective in TGF-beta receptors I and II.
Selection of mutant Mv1Lu mink lung epithelial cells resistant to growth inhibition by transforming growth factor-beta (TGF-beta) has led to the isolation of cell clones with distinct alterations in type I and II TGF-beta receptors. Certain mutant clones present a decreased number or complete loss of detectable type I receptor. Other clones show a loss and/or altered electrophoretic mobility of the type II receptor, with concomitant loss of the type I receptor. Using somatic cell hybridization analysis we demonstrate the recessive nature of these mutants with respect to the wild-type phenotype and define various mutant complementation groups. Among these, hybrids between cells that express only type II receptor (R mutants) and cells that express neither receptor type (DRa mutants) rescue wild-type expression of type I receptors. Moreover, these hybrids regain full responsiveness to TGF-beta 1, as measured by inhibition of DNA synthesis as well as stimulation of fibronectin and plasminogen activator inhibitor-1 production. These results provide evidence for an interaction between TGF-beta receptor components I and II and show that, in Mv1Lu cells, expression of both receptor types is required for mediation of biological responses to TGF-beta 1.
Laiho
M
M
Cell Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Weis
F M
FM
Boyd
F T
FT
Ignotz
R A
RA
Massagué
J
J
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D005353:Fibronectins / Q000378:metabolism; D005808:Genes, Recessive; D005816:Genetic Complementation Test; D006822:Hybrid Cells; D066298:In Vitro Techniques; D008907:Mink; D015849:Plasminogen Inactivators / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000502:physiology*; D018125:Receptors, Transforming Growth Factor beta; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000494:pharmacology / Q000502:physiology*
D005353:Fibronectins; D015849:Plasminogen Inactivators; D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta