An active Src kinase-beta-actin association is linked to actin dynamics at the periphery of colon cancer cells

Egle Avizienyte, Melanie Keppler, Emma Sandilands, Valerie G Brunton, Steve J Winder, Tony Ng, Margaret C Frame

Research output: Contribution to journalArticlepeer-review

Abstract

Src controls the dynamic actin cytoskeleton in fibroblasts and in cancer cells, although it is not known how direct its effects are. Using FRET/FLIM imaging, we found that wild type Src associates directly, or indirectly, with peripheral beta-actin at integrin adhesions after serum stimulation, and that an active Src kinase domain is essential. Beta-actin can be directly tyrosine-phosphorylated by Src in vitro, and in a Src-dependent manner in cells. Moreover, beta-actin dynamics are suppressed when Src is rendered kinase-inactive. Surprisingly, debilitating mutations in the Src SH2 or SH3 domains do not suppress association of Src with beta-actin. This may therefore be an example of a spatially regulated Src kinase/substrate interaction that is controlling peripheral actin dynamics. Interestingly, there is no FRET between Src and beta-actin at cadherin-mediated cell-cell contacts, despite apparent co-localization there, demonstrating precise spatial specificity of Src/beta-actin complexes.
Original languageEnglish
Pages (from-to)3175-88
Number of pages14
JournalExperimental Cell Research
Volume313
Issue number15
DOIs
Publication statusPublished - 10 Sep 2007

Keywords

  • Actins
  • Amino Acid Sequence
  • Cell Communication
  • Cell Line, Tumor
  • Colonic Neoplasms
  • Cytoskeletal Proteins
  • Cytoskeleton
  • Enzyme Activation
  • Fluorescence Resonance Energy Transfer
  • Humans
  • Molecular Sequence Data
  • Mutation
  • Phosphorylation
  • Protein Binding
  • Signal Transduction
  • src Homology Domains
  • src-Family Kinases

Fingerprint Dive into the research topics of 'An active Src kinase-beta-actin association is linked to actin dynamics at the periphery of colon cancer cells'. Together they form a unique fingerprint.

Cite this