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PMID:2790960

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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

Significance

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

See also

References

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