No requirement for Src family kinases for PDGF signaling in fibroblasts expressing SV40 large T antigen

Martin A. Broome, Sara Courtneidge

Research output: Contribution to journalArticle

42 Citations (Scopus)

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. What is the reason for this discrepancy? We noted that Klinghoffer et al. 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 large T 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.

Original languageEnglish (US)
Pages (from-to)2867-2869
Number of pages3
JournalOncogene
Volume19
Issue number24
StatePublished - Jun 1 2000
Externally publishedYes

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Polyomavirus Transforming Antigens
src-Family Kinases
Viral Tumor Antigens
Platelet-Derived Growth Factor
Fibroblasts
Embryonic Structures
Platelet-Derived Growth Factor Receptors
Cell Line
DNA
Intercellular Signaling Peptides and Proteins
Injections
Antibodies
Growth

Keywords

  • Mitogenesis
  • p53
  • PDGF
  • Src

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

No requirement for Src family kinases for PDGF signaling in fibroblasts expressing SV40 large T antigen. / Broome, Martin A.; Courtneidge, Sara.

In: Oncogene, Vol. 19, No. 24, 01.06.2000, p. 2867-2869.

Research output: Contribution to journalArticle

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