Conservation of function of Drosophila melanogaster abl and murine v-abl proteins in transformation of mammalian cells

Gina D. Holland, Mark J. Henkemeyer, Donal A. Kaehler, F. Michael Hoffmann, Rex Risser

Research output: Contribution to journalArticle

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Abstract

The Drosophila melanogaster abl and the murine v-abl genes encode tyrosine protein kinases (TPKs) whose amino acid sequences are highly conserved. To assess functional conservation between the two gene products, we constructed Drosophila abl/v-abl-chimeric Abelson murine leukemia viruses. In these chimeric Abelson murine leukemia viruses, the TPK and carboxy-terminal regions of v-abl were replaced with the corresponding regions of D. melanogaster abl. The chimeric Abelson murine leukemia viruses were able to mediate morphological and oncogenic transformation of NIH 3T3 cells and were able to abrogate the interleukin-3 dependence of a lymphoid cell line. We also found that a virus that contained both TPK and carboxy-terminal Drosophila abl regions had no in vitro transforming activity for primary bone marrow cells and lacked the ability to induce tumors in susceptible mice. A virus that replaced only a portion of the v-abl TPK region with that of Drosophila abl had low activity in in vitro bone marrow transformation and tumorigenesis assays. These results indicate that the transforming functions of abl TPKs are only partially conserved through evolution. These results also imply that the TPK region of v-abl is a major determinant of its efficient lymphoid cell-transforming activity.

Original languageEnglish (US)
Pages (from-to)2226-2235
Number of pages10
JournalJournal of Virology
Volume64
Issue number5
StatePublished - 1990

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Oncogene Proteins v-abl
protein-tyrosine kinases
Drosophila melanogaster
Protein-Tyrosine Kinases
Abelson murine leukemia virus
Murine leukemia virus
mice
Drosophila
proteins
cells
abl Genes
Lymphocytes
interleukin-3
Viruses
NIH 3T3 Cells
viruses
Interleukin-3
bone marrow cells
Bone Marrow Cells
bone marrow

ASJC Scopus subject areas

  • Immunology

Cite this

Conservation of function of Drosophila melanogaster abl and murine v-abl proteins in transformation of mammalian cells. / Holland, Gina D.; Henkemeyer, Mark J.; Kaehler, Donal A.; Hoffmann, F. Michael; Risser, Rex.

In: Journal of Virology, Vol. 64, No. 5, 1990, p. 2226-2235.

Research output: Contribution to journalArticle

Holland, Gina D. ; Henkemeyer, Mark J. ; Kaehler, Donal A. ; Hoffmann, F. Michael ; Risser, Rex. / Conservation of function of Drosophila melanogaster abl and murine v-abl proteins in transformation of mammalian cells. In: Journal of Virology. 1990 ; Vol. 64, No. 5. pp. 2226-2235.
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