The Fer tyrosine kinase is important for platelet-derived growth factor-BB-induced signal transducer and activator of transcription 3 (STAT3) protein phosphorylation, colony formation in soft agar, and tumor growth in vivo.
J Biol Chem
; 288(22): 15736-44, 2013 May 31.
Article
em En
| MEDLINE
| ID: mdl-23589302
ABSTRACT
Fer is a cytoplasmic tyrosine kinase that is activated in response to platelet-derived growth factor (PDGF) stimulation. In the present report, we show that Fer associates with the activated PDGF ß-receptor (PDGFRß) through multiple autophosphorylation sites, i.e. Tyr-579, Tyr-581, Tyr-740, and Tyr-1021. Using low molecular weight inhibitors, we found that PDGF-BB-induced Fer activation is dependent on PDGFRß kinase activity, but not on the enzymatic activity of Src or Jak kinases. In cells in which Fer was down-regulated using siRNA, PDGF-BB was unable to induce phosphorylation of STAT3, whereas phosphorylations of STAT5, ERK1/2, and Akt were unaffected. PDGF-BB-induced activation of STAT3 occurred also in cells expressing kinase-dead Fer, suggesting a kinase-independent adaptor role of Fer. Expression of Fer was dispensable for PDGF-BB-induced proliferation and migration but essential for colony formation in soft agar. Tumor growth in vivo was delayed in cells depleted of Fer expression. Our data suggest a critical role of Fer in PDGF-BB-induced STAT3 activation and cell transformation.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Proteínas Tirosina Quinases
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Movimento Celular
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Proteínas Proto-Oncogênicas c-sis
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Indutores da Angiogênese
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Proliferação de Células
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Fator de Transcrição STAT3
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Neoplasias
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article