Src kinase modulates the activation, transport and signalling dynamics of fibroblast growth factor receptors

Emma Sandilands, Shiva Akbarzadeh, Anna Vecchione, David G McEwan, Margaret C Frame, John K Heath

Research output: Contribution to journalArticlepeer-review


The non-receptor tyrosine kinase Src is recruited to activated fibroblast growth factor receptor (FGFR) complexes through the adaptor protein factor receptor substrate 2 (FRS2). Here, we show that Src kinase activity has a crucial role in the regulation of FGFR1 signalling dynamics. Following receptor activation by ligand binding, activated Src is colocalized with activated FGFR1 at the plasma membrane. This localization requires both active Src and FGFR1 kinases, which are inter-dependent. Internalization of activated FGFR1 is associated with release from complexes containing activated Src. Src-mediated transport and subsequent activation of FGFR1 require both RhoB endosomes and an intact actin cytoskeleton. Chemical and genetic inhibition studies showed strikingly different requirements for Src family kinases in FGFR1-mediated signalling; activation of the phosphoinositide-3 kinase-Akt pathway is severely attenuated, whereas activation of the extracellular signal-regulated kinase pathway is delayed in its initial phase and fails to attenuate.
Original languageEnglish
Pages (from-to)1162-9
Number of pages8
JournalEMBO Reports
Issue number12
Publication statusPublished - Dec 2007


  • Animals
  • Cell Membrane
  • Cells, Cultured
  • Endosomes
  • Fibroblast Growth Factor 2
  • Green Fluorescent Proteins
  • Immunoblotting
  • Mice
  • Microscopy, Confocal
  • Mutation
  • Protein Transport
  • Receptor, Fibroblast Growth Factor, Type 1
  • Recombinant Fusion Proteins
  • Signal Transduction
  • Transfection
  • src-Family Kinases

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