Activation of Src kinases p53/56(lyn) and p59(hck) by p210(bcr/abl) in myeloid cells

Susanne Danhauser-Riedl, Markus Warmuth, Brian Druker, Bertold Emmerich, Michael Hallek

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Abstract

Chronic myeloid leukemia is characterized by the Philadelphia (Ph1) translocation t(9;22) that generates a hybrid gene, bcr/abl, translated to a M(r)210,000 tyrosine kinase (p210(bcr/abl)) with transforming activity for hematopoietic cells. Hematopoietic cell transformation by p210(bcr/abl) seems to involve activation of the Ras signaling pathway by at least two different signaling intermediates, growth factor receptor-bound protein 2 and Src homology and collagen protein, but additional signaling proteins are likely to be required as well. In an effort to identify additional phosphoproteins activated by p210(bcr/abl), we studied the murine, interleukin 3-dependent, myeloid cell line, 32D, and a bcr/abl-transfected, factor-independent subline, 32Dp210. The analysis of whole-cell lysates of 32D and 32Dp210 cells showed that several proteins with a molecular weight of M(r)50,000-60,000 were phosphorylated on tyrosine residues in 32Dp210 cells. Because Src family kinases have an apparent molecular weight of M(r)50,000-60,000, we asked whether they could become activated by p210(bcr/abl). Two Src family kinases, p53/56(lyn) and p59(hck), showed a severalfold higher phosphokinase activity in 32Dp210 cells than in 32D cells. Coimmunoprecipitation experiments with anti-Lyn, anti-Hck, and anti-Abl antibodies demonstrated an intracellular association of p210(bcr/abl) with p53/56(lyn) and p59(hck). Moreover, the phosphokinase activity of p53/56(lyn) was higher in bcr/abl-positive myeloid cell lines (K562, BV173, and LAMA84) than in the bcr/abl-negative myeloid cell line JOSK-M. In conclusion, the results show that p210(bcr/abl) induces the activation of at least two Src family kinases, p53/56(lyn) and p59(hck) in myeloid cells. These findings extend the range of potential targets of p210(bcr/abl) that might mediate its transforming effects.

Original languageEnglish (US)
Pages (from-to)3589-3596
Number of pages8
JournalCancer Research
Volume56
Issue number15
StatePublished - Aug 1 1996

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src-Family Kinases
Myeloid Cells
Cell Line
GRB2 Adaptor Protein
Phosphotransferases
bcr-abl Fusion Proteins
Molecular Weight
abl Genes
Proteins
Interleukin-3
Phosphoproteins
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Tyrosine
Anti-Idiotypic Antibodies
Collagen

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Danhauser-Riedl, S., Warmuth, M., Druker, B., Emmerich, B., & Hallek, M. (1996). Activation of Src kinases p53/56(lyn) and p59(hck) by p210(bcr/abl) in myeloid cells. Cancer Research, 56(15), 3589-3596.

Activation of Src kinases p53/56(lyn) and p59(hck) by p210(bcr/abl) in myeloid cells. / Danhauser-Riedl, Susanne; Warmuth, Markus; Druker, Brian; Emmerich, Bertold; Hallek, Michael.

In: Cancer Research, Vol. 56, No. 15, 01.08.1996, p. 3589-3596.

Research output: Contribution to journalArticle

Danhauser-Riedl, S, Warmuth, M, Druker, B, Emmerich, B & Hallek, M 1996, 'Activation of Src kinases p53/56(lyn) and p59(hck) by p210(bcr/abl) in myeloid cells', Cancer Research, vol. 56, no. 15, pp. 3589-3596.
Danhauser-Riedl S, Warmuth M, Druker B, Emmerich B, Hallek M. Activation of Src kinases p53/56(lyn) and p59(hck) by p210(bcr/abl) in myeloid cells. Cancer Research. 1996 Aug 1;56(15):3589-3596.
Danhauser-Riedl, Susanne ; Warmuth, Markus ; Druker, Brian ; Emmerich, Bertold ; Hallek, Michael. / Activation of Src kinases p53/56(lyn) and p59(hck) by p210(bcr/abl) in myeloid cells. In: Cancer Research. 1996 ; Vol. 56, No. 15. pp. 3589-3596.
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abstract = "Chronic myeloid leukemia is characterized by the Philadelphia (Ph1) translocation t(9;22) that generates a hybrid gene, bcr/abl, translated to a M(r)210,000 tyrosine kinase (p210(bcr/abl)) with transforming activity for hematopoietic cells. Hematopoietic cell transformation by p210(bcr/abl) seems to involve activation of the Ras signaling pathway by at least two different signaling intermediates, growth factor receptor-bound protein 2 and Src homology and collagen protein, but additional signaling proteins are likely to be required as well. In an effort to identify additional phosphoproteins activated by p210(bcr/abl), we studied the murine, interleukin 3-dependent, myeloid cell line, 32D, and a bcr/abl-transfected, factor-independent subline, 32Dp210. The analysis of whole-cell lysates of 32D and 32Dp210 cells showed that several proteins with a molecular weight of M(r)50,000-60,000 were phosphorylated on tyrosine residues in 32Dp210 cells. Because Src family kinases have an apparent molecular weight of M(r)50,000-60,000, we asked whether they could become activated by p210(bcr/abl). Two Src family kinases, p53/56(lyn) and p59(hck), showed a severalfold higher phosphokinase activity in 32Dp210 cells than in 32D cells. Coimmunoprecipitation experiments with anti-Lyn, anti-Hck, and anti-Abl antibodies demonstrated an intracellular association of p210(bcr/abl) with p53/56(lyn) and p59(hck). Moreover, the phosphokinase activity of p53/56(lyn) was higher in bcr/abl-positive myeloid cell lines (K562, BV173, and LAMA84) than in the bcr/abl-negative myeloid cell line JOSK-M. In conclusion, the results show that p210(bcr/abl) induces the activation of at least two Src family kinases, p53/56(lyn) and p59(hck) in myeloid cells. These findings extend the range of potential targets of p210(bcr/abl) that might mediate its transforming effects.",
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N2 - Chronic myeloid leukemia is characterized by the Philadelphia (Ph1) translocation t(9;22) that generates a hybrid gene, bcr/abl, translated to a M(r)210,000 tyrosine kinase (p210(bcr/abl)) with transforming activity for hematopoietic cells. Hematopoietic cell transformation by p210(bcr/abl) seems to involve activation of the Ras signaling pathway by at least two different signaling intermediates, growth factor receptor-bound protein 2 and Src homology and collagen protein, but additional signaling proteins are likely to be required as well. In an effort to identify additional phosphoproteins activated by p210(bcr/abl), we studied the murine, interleukin 3-dependent, myeloid cell line, 32D, and a bcr/abl-transfected, factor-independent subline, 32Dp210. The analysis of whole-cell lysates of 32D and 32Dp210 cells showed that several proteins with a molecular weight of M(r)50,000-60,000 were phosphorylated on tyrosine residues in 32Dp210 cells. Because Src family kinases have an apparent molecular weight of M(r)50,000-60,000, we asked whether they could become activated by p210(bcr/abl). Two Src family kinases, p53/56(lyn) and p59(hck), showed a severalfold higher phosphokinase activity in 32Dp210 cells than in 32D cells. Coimmunoprecipitation experiments with anti-Lyn, anti-Hck, and anti-Abl antibodies demonstrated an intracellular association of p210(bcr/abl) with p53/56(lyn) and p59(hck). Moreover, the phosphokinase activity of p53/56(lyn) was higher in bcr/abl-positive myeloid cell lines (K562, BV173, and LAMA84) than in the bcr/abl-negative myeloid cell line JOSK-M. In conclusion, the results show that p210(bcr/abl) induces the activation of at least two Src family kinases, p53/56(lyn) and p59(hck) in myeloid cells. These findings extend the range of potential targets of p210(bcr/abl) that might mediate its transforming effects.

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