Epidermal growth factor-induced activation and translocation of c-Src to the cytoskeleton depends on the actin binding domain of the EGF-receptor.
In the epidermal growth factor (EGF)-receptor signal transduction cascade, the non-receptor tyrosine kinase c-Src has been demonstrated to become activated upon EGF stimulation. In this paper we show that c-Src associates with the cytoskeleton and co-isolates with actin filaments upon EGF treatment of NIH-3T3 cells transfected with the EGF receptor. Immunofluorescence studies using CLSM show colocalization of F-actin and endogenous c-Src predominantly around endosomes and not on stress fibers and cell-cell contacts. Stimulation of EGF receptor-transfected NIH-3T3 cells with EGF induces an activation and translocation of c-Src to the cytoskeleton. These processes depend upon the presence of the actin binding domain of the EGF-receptor since in cells that express EGF-receptors lacking this domain, EGF fails to induce an activation and translocation to the cytoskeleton of c-Src. These data suggest a role for the actin binding domain of the EGF-receptor in the translocation of c-Src.
Van der Heyden
M A
MA
Department of Molecular Cell Biology, Utrecht University, The Netherlands.
Oude Weernink
P A
PA
Van Oirschot
B A
BA
Van Bergen en Henegouwen
P M
PM
Boonstra
J
J
Rijksen
G
G
D016475:3T3 Cells; D008841:Actin Cytoskeleton / Q000737:chemistry / Q000201:enzymology; D000199:Actins / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D003599:Cytoskeleton / Q000378:metabolism*; D011992:Endosomes / Q000737:chemistry / Q000201:enzymology; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000032:analysis / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D000199:Actins; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D016392:Proto-Oncogene Proteins pp60(c-src)