Abstract
A growing body of literature suggests that the ubiquitously expressed Src family kinases (Src, Fyn and Yes) are required for agents such as platelet-derived growth factor (PDGF) to stimulate DNA synthesis. Yet Klinghoffer and colleagues recently presented evidence that fibroblasts derived from mice null for Src, Fyn and Yes responded normally to PDGF (Klinghoffer et al., 1999, EMBO J., 18: 2459–2471). What is the reason for this discrepancy? We noted that Klinghoffer et al. (1999) used SV40 large T antigen (largeT) to facilitate derivation of cell lines from the embryos. We therefore tested the effect of largeT on PDGF receptor signaling. We found that expression of largeT overcame the inhibitory effects of interfering forms of both Ras (N17Ras) and Src (SrcK−). Furthermore, injection of SrcK− or the cst.1 antibody (which inhibits Src, Fyn and Yes) failed to inhibit PDGF-stimulated DNA synthesis in NIH3T3 cells expressing dominant negative p53, and fibroblasts derived from p53 null embryos. These data suggest firstly that caution should be used in interpretation of experiments conducted in cell lines expressing largeT, and secondly that the role of Src family kinases in growth factor signaling may be to oppose the effects of negative growth regulators such as p53.
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Acknowledgements
We are indebted to Martine Roussel and Frederique Zindy for providing us with wild type and p53-deficient mouse embryo fibroblasts. We thank Jim Bischoff for providing us with the dominant negative p53 expression construct, Walter Eckhart for the SV40 large T antigen expression construct and Ed Harlow for the monoclonal antibody to SV40 large T.
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Broome, M., Courtneidge, S. No requirement for Src family kinases for PDGF signaling in fibroblasts expressing SV40 large T antigen. Oncogene 19, 2867–2869 (2000). https://doi.org/10.1038/sj.onc.1203608
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DOI: https://doi.org/10.1038/sj.onc.1203608
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