A role for the cytoskeleton in STAT5 activation
in MCF7 human breast cancer cells stimulated with EGF.
Lopez-Perez M, Salazar
EP.
Departamento de Biologia Celular,
Cinvestav-IPN, Av IPN# 2508, San Pedro Zacatenco, Mexico, DF 07360, Mexico.
A rapid increase in the tyrosine phosphorylation
of signal transducers and activators of transcription (STAT) proteins has
been extensively documented in cells stimulated with cytokines and growth
factors. However, the mechanisms by which these transcription factors translocate to the nucleus have not been studied in
detail. Our results demonstrate that stimulation of MCF7 cells with
epidermal growth factor (EGF) promoted an increase in the phosphorylation of STAT5 at Tyr-694, as revealed by
site-specific antibodies that recognized the phosphorylated
state of this residue. In addition, EGF stimulated STAT5 nuclear
translocation and an increased in STAT5 DNA binding activity. Prevention of
microtubules and microfilaments polymerization induced a partial inhibition
of STAT5 nuclear translocation and STAT5 DNA binding activity. However,
STAT5 phosphorylation at Tyr-694 was dependent on
the integrity of microtubule network and it was independent of the
integrity of actin cytoskeleton. Furthermore, EGF
induced the formation of the associations STAT5-tubulin and STAT5-kinesin
heavy chain in a fashion dependent of cytoskeleton integrity. In summary,
our results demonstrate, for the first time, that cytoskeleton plays an
important role in STAT5 activation and translocation into the nucleus in
MCF7 cells stimulated with EGF.
PMID: 16765629 [PubMed - as supplied by publisher
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Breast Cancer
