PMID:2790960

Citation	Chen, WS, Lazar, CS, Lund, KA, Welsh, JB, Chang, CP, Walton, GM, Der, CJ, Wiley, HS, Gill, GN and Rosenfeld, MG (1989) Functional independence of the epidermal growth factor receptor from a domain required for ligand-induced internalization and calcium regulation. Cell 59:33-43
Abstract	We have located the distal boundary of the tyrosine kinase domain of the EGF receptor and have identified a distinct sequence in the C' terminus required for EGF-dependent receptor internalization, leading to receptor down-regulation and degradation. Within this receptor domain, an 18 amino acid highly negatively charged region of predicted helical structure is required both for endocytosis via a high-affinity, saturable pathway and for ligand-stimulated increases in cytosolic calcium. In contrast to kinase-inactive, internalization-competent receptors, kinase-active, internalization-defective receptors effectively signaled gene transcription, morphological transformation, and growth. These observations support the hypothesis that mitogenic responses to EGF are mediated by activation of the intrinsic protein tyrosine kinase activity of the membrane-bound receptor, with ligand-induced internalization serving to terminate the signal.
Links	PubMed
Keywords	Amino Acid Sequence; Animals; Calcium/metabolism; Calcium/physiology; Cell Line; Down-Regulation; Endocytosis; Enzyme Activation; Humans; Kinetics; Mice; Molecular Sequence Data; Protein-Tyrosine Kinases/metabolism; Protein-Tyrosine Kinases/physiology; Receptor, Epidermal Growth Factor/metabolism; Receptor, Epidermal Growth Factor/physiology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:EGFR	enables	GO:0005515: protein binding	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:P01133	F		Seeded From UniProt	complete
HUMAN:EGF	enables	GO:0005515: protein binding	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:P00533	F		Seeded From UniProt	complete
HUMAN:EGFR_original		GO:0007173: epidermal growth factor receptor signaling pathway	NAS: Non-traceable Author Statement: :	P
HUMAN:EGFR_original		GO:0007173: epidermal growth factor receptor signaling pathway	NAS: Non-traceable Author Statement:	P
HUMAN:EGFR_original		GO:0005006: epidermal growth factor receptor activity	NAS: Non-traceable Author Statement:	F
HUMAN:EGFR	enables	GO:0005006: epidermal growth factor-activated receptor activity	ECO:0000303: author statement without traceable support used in manual assertion		F		Seeded From UniProt	complete

References

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