Targeted proteolysis of the focal adhesion kinase pp125 FAK during c-MYC-induced apoptosis is suppressed by integrin signalling

D H Crouch, V J Fincham, M C Frame

Research output: Contribution to journalArticlepeer-review

Abstract

The product of the c-myc proto-oncogene has a central role in induction of apoptosis, a physiological form of cell death characterised in vitro by morphological rounding, detachment and nuclear disintegration. Induction of apoptosis by serum withdrawal from c-Myc-transformed chicken embryo fibroblasts (CEF) results in early proteolysis of focal adhesion kinase (ppl25FAK), a tyrosine kinase implicated in the conversion of integrin signals into their biological responses. Proteolysis of pp125 FAK occurs in adherent cells prior to commitment to death, suggesting that it contributes to c-Myc-induced apoptosis, rather than being a consequence of it. Furthermore, c-Myc-induced detachment, cell death and cleavage of pp125FAK are coordinately suppressed by treating with insulin or plating on the extracellular matrix components collagen and fibronectin. In addition, proteolysis of pp125FAK is suppressed by a beta1-specific integrin antibody, which promotes cell survival in the face of the oncoprotein-induced signal for apoptosis. These results provide compelling evidence that the c-Myc-induced cell death programme in CEF requires disruption of the integrin signalling pathways which normally function when cells are spread on ECM, and that maintaining cellular pp125FAK, which couples integrins to their downstream effectors, is closely linked to cell survival.
Original languageEnglish
Pages (from-to)2689-96
Number of pages8
JournalOncogene
Volume12
Issue number12
Publication statusPublished - 20 Jun 1996

Keywords

  • Animals
  • Antibodies
  • Antigens, CD29
  • Apoptosis
  • Cell Adhesion
  • Cell Adhesion Molecules
  • Cell Death
  • Cell Line, Transformed
  • Cell Transformation, Neoplastic
  • Chick Embryo
  • Collagen
  • Culture Media, Serum-Free
  • Extracellular Matrix
  • Fibroblasts
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • Gene Expression Regulation, Neoplastic
  • Genes, myc
  • Protein-Tyrosine Kinases
  • Signal Transduction

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