The antiproliferative effect of type beta transforming growth factor occurs at a level distal from receptors for growth-activating factors.
Transforming growth factor-beta (TGF beta) from human platelets blocks the ability of Mv1Lu mink lung epithelial cells to grow in response to serum mitogens, epidermal growth factor (EGF), or insulin. The phenotypic response of Mv1Lu cells to TGF beta is characterized by a flat, very enlarged cell morphology and a markedly increased production and accumulation of extracellular matrix fibronectin. The ability of TGF beta to alter the ligand binding or signal transducing activity of mitogen receptors in Mv1Lu cells has been examined. In contrast to NRK-49F rat fibroblasts, Mv1Lu cells do not respond to TGF beta with a decrease in the affinity or a change in the number of cell surface receptors for EGF. Soluble extracts from Mv1Lu cells contain a protein kinase activity which selectively phosphorylates ribosomal protein S6; this S6 kinase activity is elevated severalfold minutes after exposure of cells to mitogens. This kinase activity has been used as the parameter to measure the signaling ability of EGF receptors and insulin receptors in cells treated with TGF beta. We find that TGF beta does not alter the basal level of S6 kinase activity or its elevation by EGF or insulin. In TGF beta-treated cells rendered insensitive to the growth-promoting action of EGF, the parameters of elevation of S6 kinase activity by EGF are similar to those of control, growth-competent cells. The results suggest that TGF beta inhibits cell proliferation by acting at a level distal from the receptors for growth-activating factors.
D000818:Animals; D001792:Blood Platelets / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D066246:ErbB Receptors / Q000378:metabolism*; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008168:Lung / Q000166:cytology* / Q000187:drug effects; D008907:Mink; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology*; D011972:Receptor, Insulin / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor; D018125:Receptors, Transforming Growth Factor beta; D015291:Transforming Growth Factors
D006133:Growth Substances; D010455:Peptides; D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta; D015291:Transforming Growth Factors; D066246:ErbB Receptors; D011972:Receptor, Insulin; D017479:Receptors, Platelet-Derived Growth Factor