RhoB and actin polymerization coordinate Src activation with endosome-mediated delivery to the membrane

Emma Sandilands, Christophe Cans, Valerie J Fincham, Valerie G Brunton, Harry Mellor, George C Prendergast, Jim C Norman, Giulio Superti-Furga, Margaret C Frame

Research output: Contribution to journalArticlepeer-review

Abstract

We have used a c-Src-GFP fusion protein to address the spatial control of Src activation and the nature of Src-associated intracellular structures during stimulus-induced transit to the membrane. Src is activated during transit, particularly in RhoB-containing cytoplasmic endosomes associated with the perinuclear recycling compartment. Knocking out RhoB or expressing a dominant-interfering Rab11 mutant suppresses both catalytic activation of Src and translocation of active kinase to peripheral membrane structures. In addition, the Src- and RhoB-containing endosomes harbor proteins involved in actin polymerization and filament assembly, for example Scar1, and newly polymerized actin can associate with these endosomes in a Src-dependent manner. This implies that Src may regulate an endosome-associated actin nucleation activity. In keeping with this, Src controls the actin dependence of RhoB endosome movement toward the plasma membrane. This work identifies RhoB as a component of "outside-in" signaling pathways that coordinate Src activation with translocation to transmembrane receptors.
Original languageEnglish
Pages (from-to)855-69
Number of pages15
JournalDevelopmental Cell
Volume7
Issue number6
DOIs
Publication statusPublished - Dec 2004

Keywords

  • 3T3 Cells
  • Actins
  • Animals
  • Catalysis
  • Cell Adhesion
  • Cell Membrane
  • Cell Nucleus
  • Cytoplasm
  • Cytoskeleton
  • Dose-Response Relationship, Drug
  • Endosomes
  • Fibronectins
  • Genes, Dominant
  • Green Fluorescent Proteins
  • Immunoprecipitation
  • Mice
  • Microscopy, Fluorescence
  • Plasmids
  • Platelet-Derived Growth Factor
  • Protein Transport
  • Recombinant Fusion Proteins
  • Signal Transduction
  • rab GTP-Binding Proteins
  • rhoB GTP-Binding Protein
  • src-Family Kinases

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