Requirement for the adapter protein GRB2 in EGF receptor endocytosis.
Activated epidermal growth factor (EGF) receptors induce the formation of various complexes of intracellular signaling proteins that are mediated by SRC homology 2 (SH2) and SH3 domains. The activated receptors are also rapidly internalized into the endocytotic compartment and degraded in lysosomes. EGF stimulation of canine epithelial cells induced a rapid and transient association of the SH3-SH2-SH3 protein GRB2 with dynamin, a guanosine triphosphatase that regulates endocytosis. Disruption of GRB2 interactions by microinjection of a peptide corresponding to the GRB2 SH2 domain or its phosphopeptide ligand blocked EGF receptor endocytosis; other SH2 domains that bind EGF receptors or antibodies that neutralize RAS did not. Both activation and termination of EGF signaling appear to be regulated by the diverse interactions of GRB2.
Wang
Z
Z
Banting and Best Department of Medical Research, University of Toronto, Canada.
Moran
M F
MF
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000911:Antibodies, Monoclonal; D002460:Cell Line; D004285:Dogs; D034281:Dynamins; D004705:Endocytosis / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism*; D051380:GRB2 Adaptor Protein; D020558:GTP Phosphohydrolases / Q000378:metabolism; D008845:Microinjections; D010446:Peptide Fragments / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism*; D011990:Receptors, Transferrin / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D015398:Signal Transduction; D018631:ras Proteins / Q000276:immunology / Q000502:physiology; D018909:src Homology Domains / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D000911:Antibodies, Monoclonal; D051380:GRB2 Adaptor Protein; D010446:Peptide Fragments; D011506:Proteins; D011990:Receptors, Transferrin; D011993:Recombinant Fusion Proteins; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D020558:GTP Phosphohydrolases; D018631:ras Proteins; D034281:Dynamins