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Differences in inhibition by IDF 45 (an inhibitory diffusible factor) of early RNA synthesis stimulation induced by pp60 v‐src and various mitogens
Author(s) -
Delbe J.,
Villaudy J.,
Blat C.,
Desauty G.,
Golde A.,
Harel L.
Publication year - 1990
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041420219
Subject(s) - dna synthesis , rna , stimulation , dna , microbiology and biotechnology , growth factor , proto oncogene tyrosine protein kinase src , gene expression , cell growth , biology , chemistry , gene , biochemistry , receptor , endocrinology , signal transduction
Factors inhibiting cell growth have been isolated from different cell types. However, little information is available concerning their mode of action. A novel growth inhibitory factor of 45 kDa (IDF 45 ) was recently purified to homogeneity from medium conditioned by 3T3 cells. This molecule was able to inhibit DNA synthesis and the growth of chick embryo fibroblasts (CEF) in a reversible manner. By contrast, DNA synthesis stimulated by v‐src expression in CEF was poorly inhibited by IDF 45 . In order to gain further insight into the IDF 45 mode of action in normal and transformed CEF, we compared the effects of IDF 45 on early stimulation of RNA synthesis induced in CEF by different mitogenic factors and by v‐src gene expression. Stimulation, by serum, of RNA synthesis was inhibited by IDF 45 ; however, inhibition increased when cells were preincubated with IDF 45 before addition of serum and cell labeling for 2 h. IDF 45 was also able to inhibit partially the stimulation of RNA synthesis induced by PMA and PDGF but was unable to inhibit stimulation of RNA synthesis induced by insulin and v‐src expression. By contrast, stimulation of RNA synthesis induced by IGF‐I was rapidly 100% inhibited by IDF 45 . The effect of IDF 45 on DNA synthesis stimulated by the different mitogens was also determined and was correlated with the effect of IDF 45 on RNA synthesis. These results suggest that the modes of action of IDF 45 on stimulation of RNA synthesis by v‐src and by insulin are similar. Our present results agree with others showing the bifunctional activity of IDF 45 as an IGF‐binding protein and as an inhibitory molecule in DNA stimulation induced by serum.