Growth inhibition by transforming growth factor beta (TGF-beta) type I is restored in TGF-beta-resistant hepatoma cells after expression of TGF-beta receptor type II cDNA.
The growth of human hepatoma Hep 3B cells is potently inhibited by TGF-beta 1 (ID50 = 0.2 ng/ml, 8 pM). A mutant cell line was derived that was not inhibited in growth by TGF-beta 1 at 5 ng/ml (200 pM) and that lacked TGF-beta receptor type II (TGF-beta RII) gene. Transfection of the cloned cDNA for human TGF-beta RII to this mutant cell line restored receptor expression as well as the inhibition in growth by TGF-beta 1. In both wild-type and mutant cells stably transfected with TGF-beta RII cDNA, TGF-beta RII coimmunoprecipitated with TGF-beta receptor type I in the presence of ligand. These experiments provide direct evidence for the role of TGF-beta RII in the inhibitory effect of TGF-beta on growth and suggest that TGF-beta RII acts by means of a heteromeric surface complex with TGF-beta receptor type I.
Pittsburgh Transplantation Institute, University of Pittsburgh, PA 15260.
M
M
Inagaki
A
A
Moustakas
H Y
HY
Lin
H F
HF
Lodish
B I
BI
Carr
D000345:Affinity Labels; D000906:Antibodies; D015139:Blotting, Southern; D006528:Carcinoma, Hepatocellular; D002455:Cell Division / Q000187:drug effects*; D002462:Cell Membrane / Q000378:metabolism; D004351:Drug Resistance / Q000502:physiology*; D006801:Humans; D007457:Iodine Radioisotopes; D007700:Kinetics; D008113:Liver Neoplasms; D010957:Plasmids; D012333:RNA, Messenger / Q000302:isolation & purification / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000345:Affinity Labels; D000906:Antibodies; D007457:Iodine Radioisotopes; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta