The BCR-ABL oncogene requires both kinase activity and src-homology 2 domain to induce cytokine secretion

Steven M. Anderson, Jeanette Mladenovic

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Expression of either the BCR-ABL or the v-abl oncogene in the factor- dependent murine myeloid cell line FDCP-1 results in growth factor independence. Studies with temperature-sensitive mutants of v-abl show that this growth factor independence is oncogene dependent. Likewise, cells expressing a kinase inactive mutant of BCR-ABL did not grow in the absence of interleukin-3 (IL-3). Conditioned media from cells expressing either v-abl or BCR-ABL contained growth factor(s) capable of stimulating the proliferation of uninfected FDCP-1 cells. Based on enzyme-linked immunosorbent assay studies and antibody neutralization studies, the major growth factor present in these conditioned media is IL-3. Because of the importance of SH2 domains in regulating substrate interactions, we examined the ability of SH2 deletion mutants in BCR-ABL to induce growth factor independence. Cells expressing a mutant of BCR-ABL lacking the SH2 domain were growth factor independent; however, they did not secrete growth factors. This finding suggests that while IL-3 produced by cells infected with BCR-ABL may contribute to autocrine or paracrine growth factor independence, expression of an activated tyrosine kinase alone may be able to induce growth factor independence. Furthermore, the secretion of cytokines maybe correlated with a specific region of the BCR-ABL oncogene, suggesting that activation (phosphorylation) of specific substrates may be critical for transcriptional activation of cytokine genes.

Original languageEnglish (US)
Pages (from-to)238-244
Number of pages7
JournalBlood
Volume87
Issue number1
StatePublished - Jan 1 1996
Externally publishedYes

Fingerprint

src Homology Domains
Oncogenes
Intercellular Signaling Peptides and Proteins
Phosphotransferases
Cytokines
Interleukin-3
Cells
Conditioned Culture Medium
Chemical activation
abl Genes
Immunosorbents
Phosphorylation
Myeloid Cells
Substrates
Protein-Tyrosine Kinases
Transcriptional Activation
Assays
Genes
Enzyme-Linked Immunosorbent Assay
Cell Line

ASJC Scopus subject areas

  • Hematology

Cite this

The BCR-ABL oncogene requires both kinase activity and src-homology 2 domain to induce cytokine secretion. / Anderson, Steven M.; Mladenovic, Jeanette.

In: Blood, Vol. 87, No. 1, 01.01.1996, p. 238-244.

Research output: Contribution to journalArticle

Anderson, Steven M. ; Mladenovic, Jeanette. / The BCR-ABL oncogene requires both kinase activity and src-homology 2 domain to induce cytokine secretion. In: Blood. 1996 ; Vol. 87, No. 1. pp. 238-244.
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