Development of cellular resistance to pp60(v-src) kinase-induced cell death

Li-Wha Wu, P. B. Hackett

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The v-src gene of Rous sarcoma virus (RSV) encodes pp60(v-src), a tyrosine kinase that can initiate cellular transformation. High levels of v-src gene expression can either be cytotoxic or the cause of altered expression of cellular genes. Examination of cytotoxic thresholds is difficult because cells expressing high levels of a cytotoxic oncogene will die. To evaluate quantitatively the cytotoxicity of pp60(v-src) on growth, we amplified two different v-src genes, under the control of the human hsp70B heat shock promoter to establish cell clones with varying copy numbers of the heat-inducible v-src gene. The viability of cell lines over a prolonged period of time depended on the particular src gene, the expression of v-src mRNA, synthesis of the pp60(v-src) protein and, most importantly, the tyrosine kinase activity of the pp60(v-src) protein. We found a relatively sharp threshold in v-src-encoded tyrosine kinase activity above which cell viability rapidly declines, However, over time, tyrosine kinase activity was exponentially suppressed at about a 10-fold higher rate than pp60(v-src) protein during passage. Our results indicate that homeostasis of tyrosine phosphorylation is important for cell viability, that perturbation of this balance results in cell mortality, and that cells can evolve to accommodate overexpression of oncogene by downregulating the level of tyrosine kinase activity.

Original languageEnglish
Pages (from-to)1459-1468
Number of pages10
JournalOncogene
Volume11
Issue number8
Publication statusPublished - 1995 Jan 1

Fingerprint

Oncogene Protein pp60(v-src)
src Genes
src-Family Kinases
Cell Death
Protein-Tyrosine Kinases
Oncogenes
Gene Expression
Cell Survival
Hot Temperature
Rous sarcoma virus
Tyrosine
Shock
Homeostasis
Down-Regulation
Clone Cells
Phosphorylation
Cell Line
Messenger RNA
Mortality
Growth

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Wu, Li-Wha ; Hackett, P. B. / Development of cellular resistance to pp60(v-src) kinase-induced cell death. In: Oncogene. 1995 ; Vol. 11, No. 8. pp. 1459-1468.
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Development of cellular resistance to pp60(v-src) kinase-induced cell death. / Wu, Li-Wha; Hackett, P. B.

In: Oncogene, Vol. 11, No. 8, 01.01.1995, p. 1459-1468.

Research output: Contribution to journalArticle

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