Endocytosis and intracellular trafficking of ErbBs.
This review article describes the pathways and mechanisms of endocytosis and post-endocytic sorting of the EGF receptor (EGFR/ErbB1) and other members of the ErbB family. Growth factor binding to EGFR accelerates its internalization through clathrin-coated pits which is followed by the efficient lysosomal targeting of internalized receptors and results in receptor down-regulation. The role of EGFR interaction with the Grb2 adaptor protein and Cbl ubiquitin ligase, and receptor ubiquitination in the clathrin-dependent internalization and sorting of EGFR in multivesicular endosomes is discussed. Activation and phosphorylation of ErbB2, ErbB3 and ErbB4 also results in their ubiquitination. However, these ErbBs are internalized and targeted to lysosomes less efficiently than EGFR. When overexpressed endocytosis-impaired ErbBs may inhibit the internalization and degradation of EGFR.
Sorkin
Alexander
A
Department of Pharmacology, University of Colorado Denver Anschutz Medical Center, Aurora, Colorado 80045-0508, USA. alexander.sorkin@uchsc.edu
Goh
Lai Kuan
LK
D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002966:Clathrin / Q000378:metabolism; D022162:Cytoplasmic Vesicles / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology*; D011992:Endosomes / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D051380:GRB2 Adaptor Protein / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D018739:Oncogene Proteins v-erbB / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D002966:Clathrin; D051380:GRB2 Adaptor Protein; D018739:Oncogene Proteins v-erbB; D020033:Protein Isoforms; D004815:Epidermal Growth Factor; D066246:ErbB Receptors
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