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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. Access through
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. 1999 _Nature Cell Biol_ 1: 20–26 Download references 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. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * SUGEN Inc, 230 East Grand Avenue, South San Francisco, 94080, California, CA, USA Martin A Broome
& Sara A Courtneidge Authors * Martin A Broome View author publications You can also search for this author inPubMed Google Scholar * Sara A Courtneidge View author publications You can
also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE 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 Download citation * Received: 07
February 2000 * Revised: 06 April 2000 * Accepted: 06 April 2000 * Published: 01 June 2000 * Issue Date: 01 June 2000 * DOI: https://doi.org/10.1038/sj.onc.1203608 SHARE THIS ARTICLE Anyone
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Springer Nature SharedIt content-sharing initiative KEYWORDS * p53 * PDGF * mitogenesis * Src