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Tyrosine kinase oncogenes abrogate interleukin-3 dependence of murine myeloid cells through signaling pathways involving c-myc - conditional regulation of c-myc transcription by temperature-sensitive v-abl

Academic Article
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Overview

authors

  • Cleveland, John
  • Dean, M.
  • Rosenberg, N.
  • Wang, J. Y. J.
  • Rapp, U. R.

publication date

  • December 1989

journal

  • Molecular and Cellular Biology  Journal

abstract

  • Retroviral expression vectors carrying the tyrosine kinase oncogenes abl, fms, src, and trk abrogate the requirements of murine myeloid FDC-P1 cells for interleukin-3 (IL-3). Factor-independent clones constitutively express c-myc in the absence of IL-3, whereas in parental cultures c-myc transcription requires the presence of the ligand. To directly test the effect of a tyrosine kinase oncogene on c-myc expression, retroviral constructs containing three different temperature-sensitive mutants of v-abl were introduced into myeloid IL-3-dependent FDC-P1 and 32D cells. At the permissive temperature, clones expressing temperature-sensitive abl behaved like wild-type abl-containing cells in their growth properties and expressed c-myc constitutively. Temperature shift experiments demonstrated that both IL-3 abrogation and the regulation of c-myc expression correlated with the presence of functional v-abl. Induction of c-myc expression by reactivation of temperature-sensitive v-abl mimicked c-myc induction by IL-3 in that it did not require protein synthesis and occurred at the level of transcription, with effects on both initiation and a transcription elongation block. However, v-abl-regulated FDC-P1 cell growth differed from IL-3-regulated growth in that c-fos and junB, which are normally induced by IL-3, were not induced by activation of v-abl.

subject areas

  • Animals
  • Cell Line
  • Clone Cells
  • Gene Expression Regulation, Neoplastic
  • Interleukin-3
  • Leukemia Virus, Murine
  • Moloney murine leukemia virus
  • Oncogenes
  • Promoter Regions, Genetic
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-myc
  • Proto-Oncogenes
  • Signal Transduction
  • Temperature
  • Transcription, Genetic
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Identity

PubMed Central ID

  • PMC363740

International Standard Serial Number (ISSN)

  • 0270-7306

PubMed ID

  • 2555703
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Additional Document Info

start page

  • 5685

end page

  • 5695

volume

  • 9

issue

  • 12

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