Home LiteratureArticle Details
PMID: 2424012 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Monoclonal antibody against epidermal growth factor receptor is internalized without stimulating receptor phosphorylation.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 83 ·No. 11 ·1986-06-00 ·Pages 3825-9

Sunada H, Magun BE, Mendelsohn J, MacLeod CL

Abstract

The down-regulation and internalization of the epidermal growth factor (EGF) receptors induced by two separate anti-EGF monoclonal antibodies (mAbs), IgG1 mAb-225 and -455, and by EGF was examined. mAb-225 competitively inhibits EGF binding and it is internalized to an extent comparable to EGF. The antibody down-regulates surface EGF receptors in a dose-dependent manner. In contrast, mAb-455 does not competitively inhibit the binding of EGF or mAb-225, but it specifically immunoprecipitates the EGF receptor. mAb-455 also down-regulates the EGF receptor. Unlike EGF, which elicits phosphorylation of the receptor at tyrosine, threonine, and serine residues, neither of these antibodies elicits phosphorylation of the EGF receptor in intact A431 cells or in KB cells. Our studies suggest that EGF-stimulated phosphorylation of the receptor is not required for the internalization of the ligand-receptor complex.

MeSH Terms
Antibodies, Monoclonal/immunology Endocytosis Epidermal Growth Factor/metabolism ErbB Receptors Humans Phosphorylation Phosphotyrosine Receptors, Cell Surface/immunology,metabolism Tyrosine/analogs & derivatives,metabolism
Chemicals
Antibodies, Monoclonal Receptors, Cell Surface Phosphotyrosine Tyrosine Epidermal Growth Factor ErbB Receptors
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Sunada H
Magun B E
Mendelsohn J
MacLeod C L
References (32)
32 references, click to expand
  1. Visualization by fluorescence of the binding and internalization of epidermal growth factor in human carcinoma cells A-431.
    Proc Natl Acad Sci U S A. 1978 Jul;75(7):3317-21 PMID: 356052
  2. A direct radioimmunoassay for human epidermal growth factor receptor using 32P-autophosphorylated receptor.
    Anal Biochem. 1985 Sep;149(2):438-47 PMID: 3000217
  3. Rapid enhancement of protein phosphorylation in A-431 cell membrane preparations by epidermal growth factor.
    J Biol Chem. 1979 Jun 10;254(11):4884-91 PMID: 312292
  4. Epidermal growth factor.
    Annu Rev Biochem. 1979;48:193-216 PMID: 382984
  5. Rapid induction of morphological changes in human carcinoma cells A-431 by epidermal growth factors.
    J Cell Biol. 1979 Oct;83(1):260-5 PMID: 315943
  6. Identification of phosphotyrosine as a product of epidermal growth factor-activated protein kinase in A-431 cell membranes.
    J Biol Chem. 1980 Sep 25;255(18):8363-5 PMID: 6157683
  7. Epidermal growth factor induces rapid tyrosine phosphorylation of proteins in A431 human tumor cells.
    Cell. 1981 Jun;24(3):741-52 PMID: 6166387
  8. Increased phosphotyrosine content and inhibition of proliferation in EGF-treated A431 cells.
    Nature. 1981 Sep 24;293(5830):305-7 PMID: 6268987
  9. Epidermal growth factor inhibits growth of A431 human epidermoid carcinoma in serum-free cell culture.
    J Cell Biol. 1982 Apr;93(1):1-4 PMID: 7040412
  10. The phosphomannosyl recognition system for intracellular and intercellular transport of lysosomal enzymes.
    J Cell Biochem. 1982;18(1):67-85 PMID: 6279685
  11. Synthesis, turnover, and down-regulation of epidermal growth factor receptors in human A431 epidermoid carcinoma cells and skin fibroblasts.
    J Biol Chem. 1982 Oct 10;257(19):11489-96 PMID: 6288686
  12. Regulation of cell proliferation by epidermal growth factor.
    CRC Crit Rev Biochem. 1983;14(2):93-111 PMID: 6301752
  13. Intracellular processing of 125I-epidermal growth factor in rat embryo fibroblasts.
    J Cell Biochem. 1982;20(3):259-76 PMID: 6984857
  14. Analysis of morphology and receptor metabolism in clonal variant A431 cells with differing growth responses to epidermal growth factor.
    J Cell Physiol. 1983 Jun;115(3):235-42 PMID: 6304117
  15. Development of a serum-free medium for growth of NS-1 mouse myeloma cells and its application to the isolation of NS-1 hybridomas.
    Anal Biochem. 1983 Apr 15;130(2):445-53 PMID: 6869833
  16. The biochemistry and physiology of the receptor-kinase for epidermal growth factor.
    Mol Cell Endocrinol. 1983 Jul;31(1):1-19 PMID: 6309581
  17. Detection and quantification of phosphotyrosine in proteins.
    Methods Enzymol. 1983;99:387-402 PMID: 6196603
  18. Expression of epidermal growth factor receptors in human brain tumors.
    Cancer Res. 1984 Feb;44(2):753-60 PMID: 6318976
  19. Growth inhibition of human tumor cells in athymic mice by anti-epidermal growth factor receptor monoclonal antibodies.
    Cancer Res. 1984 Mar;44(3):1002-7 PMID: 6318979
  20. C-kinase phosphorylates the epidermal growth factor receptor and reduces its epidermal growth factor-stimulated tyrosine protein kinase activity.
    J Biol Chem. 1984 Feb 25;259(4):2553-8 PMID: 6321473
  21. Intracellular processing of epidermal growth factor. I. Acidification of 125I-epidermal growth factor in intracellular organelles.
    J Biol Chem. 1984 Mar 10;259(5):3047-52 PMID: 6321492
  22. Amplification and enhanced expression of the epidermal growth factor receptor gene in A431 human carcinoma cells.
    Science. 1984 Apr 27;224(4647):417-9 PMID: 6200934
  23. Down-regulation of the epidermal growth factor receptor in KB cells is due to receptor internalization and subsequent degradation in lysosomes.
    Proc Natl Acad Sci U S A. 1984 Apr;81(8):2384-8 PMID: 6326124
  24. Monoclonal anti-epidermal growth factor receptor antibodies which are inhibitors of epidermal growth factor binding and antagonists of epidermal growth factor binding and antagonists of epidermal growth factor-stimulated tyrosine protein kinase activity.
    J Biol Chem. 1984 Jun 25;259(12):7755-60 PMID: 6330079
  25. Human squamous cell lung cancers express increased epidermal growth factor receptors.
    J Clin Invest. 1984 Aug;74(2):647-51 PMID: 6086719
  26. Protein kinase C phosphorylation of the EGF receptor at a threonine residue close to the cytoplasmic face of the plasma membrane.
    Nature. 1984 Oct 4-10;311(5985):480-3 PMID: 6090944
  27. Autophosphorylation sites on the epidermal growth factor receptor.
    Nature. 1984 Oct 4-10;311(5985):483-5 PMID: 6090945
  28. Immunoaffinity purification of the epidermal growth factor receptor. Stoichiometry of binding and kinetics of self-phosphorylation.
    J Biol Chem. 1984 Dec 10;259(23):14631-6 PMID: 6094567
  29. Biological effects in vitro of monoclonal antibodies to human epidermal growth factor receptors.
    Mol Biol Med. 1983 Dec;1(5):511-29 PMID: 6094961
  30. Phorbol esters induce transient internalization without degradation of unoccupied epidermal growth factor receptors.
    Proc Natl Acad Sci U S A. 1985 May;82(9):2774-8 PMID: 2859591
  31. Relationship between production of epidermal growth factor receptors, gene amplification, and chromosome 7 translocation in variant A431 cells.
    Somat Cell Mol Genet. 1985 Jul;11(4):309-18 PMID: 2410984
  32. Epidermal growth factor stimulates phosphorylation in membrane preparations in vitro.
    Nature. 1978 Nov 23;276(5686):409-10 PMID: 309559
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.83.11.3825
Published
1986-06-00
Pages
3825-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC323616
Subset
IM
Grants
NCI NIH HHS · CA29290 · United States
NCI NIH HHS · CA37778 · United States
NCI NIH HHS · CA42060 · United States
External Links
PubMed source DOI: 10.1073/pnas.83.11.3825 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2