Tyrosine phosphorylation and activation of focal adhesion kinase (p125(FAK)) by BCR-ABL oncoprotein

A. Gotoh, K. Miyazawa, K. Ohyashiki, T. Tauchi, H. S. Boswell, H. E. Broxmeyer, K. Toyama

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Abstract

Focal adhesion kinase (p125(FAK); FAK) is a protein tyrosine kinase that is tyrosine-phosphorylated in response to v-src-mediated transformation cell adhesion, and stimulation with neuropeptides. To elucidate a possible functional relationship between FAK and BCR-ABL oncoprotein detected in Philadelphia chromosome-positive (Ph+) leukemias, we investigated the tyrosine phosphorylation state of FAK in a murine growth factor-dependent cell line and in its stable human bcr-abl cDNA transfectant. In interleukin-3 (IL-3)-dependent NFS/N1.H7 cells, tyrosine phosphorylation of FAK was not detected after stimulation with either IL-3 or Steel factor (SLF), both of which involve Pas-mediated signaling pathways. However, stable gene transfection with p210(bcr-abl) cDNA into H7 cells made these cells growth factor-independent for proliferation and resulted in constitutive tyrosine phosphorylation and kinase activation of FAK. Constitutive phosphorylation and activation of PAK was also observed in all Ph+ leukemia cell lines examined-that is, K562, TS9;22, and YS9;22, which express p210(BCR-ABL), and NALM-21 and YS9;22, which express p185(BCR-ABL). Ph-negative (Ph-) cell lines, such as MO7e and JM, did not show any detectable tyrosine phosphorylation of FAK. FAK phosphorylation in BCR-ABL-expressing cells was inhibited in a dose-dependent manner by cytochalasin D, a reagent that disrupts the intracellular network of actin filaments. However, no suppression of kinase activity or protein expression of BCR-ABL was observed after treatment with cytochalasin D. A physical association between BCR-ABL and FAK was not apparent. These data suggest that BCR-ABL may be involved in the activation of FAK. Moreover, FAK may be distinct from components in Pas-mediated signaling cascades that are activated by stimulation of myeloid cells with various cytokines.

Original languageEnglish (US)
Pages (from-to)1153-1159
Number of pages7
JournalExperimental Hematology
Volume23
Issue number11
StatePublished - Jan 1 1995

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Keywords

  • BCR-ABL
  • Focal adhesion kinase
  • Signal transduction
  • Tyrosine phosphorylation

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Genetics
  • Cell Biology
  • Cancer Research

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