Cleavage of focal adhesion kinase by different proteases during SRC-regulated transformation and apoptosis. Distinct roles for calpain and caspases

N O Carragher, V J Fincham, D Riley, M C Frame

Research output: Contribution to journalArticlepeer-review

Abstract

Integrin-associated focal adhesion complexes provide the main adhesive links between the cellular actin cytoskeleton and the surrounding extracellular matrix. In vitro, cells utilize a complex temporal and spatially regulated mechanism of focal adhesion assembly and disassembly required for cell migration. Recent studies indicate that members of both calpain and caspase protease families can promote limited proteolytic cleavage of several components of focal adhesions leading to disassembly of these complexes. Such mechanisms that influence cell adhesion may be deregulated under pathological conditions characterized by increased cell motility, such as tumor invasion. v-Src-induced oncogenic transformation is associated with loss of focal adhesion structures and transition to a less adherent, more motile phenotype, while inactivating temperature-sensitive v-Src in serum-deprived transformed cells leads to detachment and apoptosis. In this report, we demonstrate that v-Src-induced disassembly of focal adhesions is accompanied by calpain-dependent proteolysis of focal adhesion kinase. Furthermore, inhibitors of calpain repress v-Src-induced focal adhesion disruption, loss of substrate adhesion, and cell migration. In contrast, focal adhesion loss during detachment and apoptosis induced after switching off temperature-sensitive v-Src in serum-deprived transformed cells is accompanied by caspase-mediated proteolysis of focal adhesion kinase. Thus, calpain and caspase differentially regulate focal adhesion turnover during Src-regulated cell transformation, motility, and apoptosis.
Original languageEnglish
Pages (from-to)4270-5
Number of pages6
JournalJournal of Biological Chemistry
Volume276
Issue number6
DOIs
Publication statusPublished - 9 Feb 2001

Keywords

  • Animals
  • Apoptosis
  • Calpain
  • Caspases
  • Cell Transformation, Viral
  • Cells, Cultured
  • Chick Embryo
  • Endopeptidases
  • Focal Adhesion Protein-Tyrosine Kinases
  • Hydrolysis
  • Immunohistochemistry
  • Oncogene Protein pp60(v-src)
  • Protein-Tyrosine Kinases

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