Modulation of pp60v‐src and pp60c‐src expression in rous sarcoma virus—transformed hamster fibroblasts transfected with activated N‐ras

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Abstract
Three phenotypically different hamster cell lines transformed with Rous sarcoma virus (RSV) were transfected with plasmid DNA containing an activated N‐ras oncogene, and nine clones expressing various levels of p21N‐ras were characterized. We examined the effects of p21N‐ras on expression and kinase activity of resident src proteins by using a variety of assays that allowed us to discriminate between viral and cellular src proteins. In eight clones with a 10‐ to 20‐fold increase in p21N‐ras levels relative to the endogenous protein, we observed a marked reduction in the synthesis and kinase activity of p60v‐src. This decrease correlated with transcriptional downregulation of RSV genomic and v‐src subgenomic mRNAs. In the same cells, we found a concomitant accumulation of p60c‐src and, accordingly, an increase in its protein kinase activity without an apparent increase in c‐src mRNA levels. Therefore, modulation of viral and cellular src proteins in cells overexpressing p21N‐ras appeared to result from two distinct effects: a downregulation of long terminal repeat—driven transcription and a more complex interaction with cellular effectors that control the stability of p60c‐src. Such modulation also seemed to depend on the levels of p21N‐ras and, possibly, on host‐cell factors, since it was not observed in the third cell line, in which the relative increase in p21N‐ras was only 2.5‐fold to fivefold.