Cited by 705HER2/EGFR in Cancer ResearchProtein Kinase Regulation and GTPase SignalingLung Cancer Treatments and Mutations

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Autophosphorylation sites on the epidermal growth factor receptor

Downward, J., Parker, P., Waterfield, M. D.·1984·Nature

DOI 10.1038/311483a0

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Abstract

The epidermal growth factor (EGF) receptor is a tyrosine-specific protein kinase with autophosphorylating activity. A 300 amino acid-long region of the receptor's cytoplasmic domain matches (35-90% homology) sequences of transforming proteins from the src family and includes a putative nucleotide binding site. Several of the src transforming proteins have tyrosine kinase activity, but v-erb-B, which appears to be a truncated EGF receptor, is virtually identical to the receptor over this region and yet lacks detectable kinase activity. To locate possible acceptor sites in the v-erb-B protein, we have mapped these sites in the human EGF receptor. We report here that three tyrosine sites near the C-terminus are phosphorylated in vitro. In intact cells, we find that EGF stimulates phosphorylation of several sites, the tyrosine 14 residues from the C-terminus being modified the most extensively. The equivalent site is absent in the v-erb-B protein of avian erythroblastosis virus (AEV) and may influence tyrosine kinase activity.

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Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells
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Self-citation

Authors: Downward, J., Parker, P., & Waterfield, M. D.
ORCID: Downward, J.
Parker, P.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 1984-10
Volume: 311
Issue: 5985
Pages: 483-485
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/311483a0
OpenAlex: W2056681493
Cited by: 704
References: 22
Citations by year: 2026: 2 · 2025: 7 · 2024: 5 · 2023: 5 · 2022: 11 · 2021: 14 · 2020: 9 · 2019: 9 · 2018: 11 · 2017: 16 · 2016: 15 · 2015: 13 · 2014: 17 · 2013: 18 · 2012: 15
FWCI: 22.58
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
Keywords: epidermal growth factor receptor, autophosphorylation, tyrosine kinase, autophosphorylation sites, avian erythroblastosis virus, receptor cytoplasmic domain, kinase activity, transforming protein
MeSH terms: Amino Acid Sequence, Epidermal Growth Factor, Humans, Phosphorylation, Receptors, Cell Surface, Tyrosine, ErbB Receptors

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Autophosphorylation sites on the epidermal growth factor receptor

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