Transforming growth factor beta (TGF‐β) inhibits hepatocyte DNA synthesis independently of EGF binding and egf receptor autophosphorylation
- 1 May 1988
- journal article
- research article
- Published by Wiley in Journal of Cellular Physiology
- Vol. 135 (2), 253-261
- https://doi.org/10.1002/jcp.1041350212
Abstract
Subpicomolar concentrations of human platelet-derived transforming growth factor beta (TGF-β) inhibited growth factor-stimulated DNA synthesis in primary cultures of adult rat hepatocytes. This inhibition was not the result of changes in the size of intracellular pools of 3H-thymidine and was not dependent on the state of confluence of the cells. A 24-hr exposure to TGF-β either before or after insulin/EGF stimulation was as inhibitory on DNA synthesis between 48 and 72 hr of culture as was TGF-β present throughout 72 hr of culture. From 12 hr in culture to 24 hr, hepatocyte EGF binding sites dropped from about 230,000 to 85,000 per cell with no significant change in Kd, but with a loss in capacity for EGF-induced receptor down-regulation. Maximally inhibitory concentrations of TGF-β did not compete with EGF for the EGF receptor, and a 4-to 24-hr exposure to TGF-β did not alter subsequent EGF binding. Coincubation of hepatocytes with TGF-β and EGF did not influence the 60% reduction in EGF binding sites produced by EGF alone. In addition, TGF-β did not prevent EGF-induced autophosphorylation of the 170,000 dalton EGF receptor in membranes form whole liver. Our studies suggest that TGF-β regulates hepatocyte growth independently of changes in EGF receptor number, ligand affinity, or postbinding autophosphorylation.Keywords
This publication has 44 references indexed in Scilit:
- Transforming growth factor β inhibits DNA synthesis in hepatocytes isolated from normal and regenerating rat liverBiochemical and Biophysical Research Communications, 1987
- The transforming growth factor-β system, a complex pattern of cross-reactive ligands and receptorsCell, 1987
- Inhibition of proliferation of cultured rat liver epithelial cells at specific cell cycle stages by transforming growth factor-βBiochemical and Biophysical Research Communications, 1987
- Partial purification and characterization of masking protein for β-type transforming growth factor from rat plateletsBiochemical and Biophysical Research Communications, 1986
- Inhibitory effect of transforming growth factor-β on DNA synthesis of adult rat hepatocytes in primary cultureBiochemical and Biophysical Research Communications, 1985
- Transforming growth factor-beta modulates the high-affinity receptors for epidermal growth factor and transforming growth factor-alpha.The Journal of cell biology, 1985
- Preparation of medium MAB87/3 for primary cultures of epithelial cellsTissue Culture Association Manual, 1977
- A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye bindingAnalytical Biochemistry, 1976
- Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4Nature, 1970
- THE ATTRACTIONS OF PROTEINS FOR SMALL MOLECULES AND IONSAnnals of the New York Academy of Sciences, 1949