title: RhoB and actin polymerization coordinate Src activation with endosome-mediated delivery to the membrane.
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.
authors.affiliation: The Beatson Institute for Cancer Research, Cancer Research UK Beatson Laboratories, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, United Kingdom.
authors.forename: Emma
authors.initials: E
authors.lastname: Sandilands
authors.forename: Christophe
authors.initials: C
authors.lastname: Cans
authors.forename: Valerie J
authors.initials: VJ
authors.lastname: Fincham
authors.forename: Valerie G
authors.initials: VG
authors.lastname: Brunton
authors.forename: Harry
authors.initials: H
authors.lastname: Mellor
authors.forename: George C
authors.initials: GC
authors.lastname: Prendergast
authors.forename: Jim C
authors.initials: JC
authors.lastname: Norman
authors.forename: Giulio
authors.initials: G
authors.lastname: Superti-Furga
authors.forename: Margaret C
authors.initials: MC
authors.lastname: Frame
mesh_terms: D016475:3T3 Cells; D000199:Actins / Q000378:metabolism*; D000818:Animals; D002384:Catalysis; D002448:Cell Adhesion; D002462:Cell Membrane / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D011992:Endosomes / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D005799:Genes, Dominant; D049452:Green Fluorescent Proteins / Q000378:metabolism; D047468:Immunoprecipitation; D051379:Mice; D008856:Microscopy, Fluorescence; D010957:Plasmids / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D020743:rhoB GTP-Binding Protein / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism*; D000099193:rab11 GTP-Binding Proteins
chemical_list: D000199:Actins; D005353:Fibronectins; D049452:Green Fluorescent Proteins; D010982:Platelet-Derived Growth Factor; D011993:Recombinant Fusion Proteins; D020691:rab GTP-Binding Proteins; D020743:rhoB GTP-Binding Protein; D019061:src-Family Kinases; D000099193:rab11 GTP-Binding Proteins