Abstract

A procedure was developed for the large-scale purification of EGF receptor from cultured human cells utilizing immunoaffinity chromatography with monoclonal anti-EGF receptor antibodies. Partial amino acid sequence (collaboration with M. Waterfield) analysis of six peptides derived from EGF receptor very closely matched a part of the deduced sequence of the V-erb-B transforming protein of avian erythroblastosis virus (AEV). The complete amino acid sequence of EGF receptor deduced from human cDNA clones (collaboration with A. Ullrich) indicated that V-erb-B protein is a truncated EGF receptor. It is proposed that the virus acquired part of the cellular gene sequence of EGF receptor. This truncated receptor lacked the external binding domain but retained the transmembrane and cytoplasmic domain involved in stimulation of cell proliferation and possesses intrinsic tyrosine kinase activity. Similar proteins are also expressed in leukemias induced by the chronic avian leukosis virus which activates the C-erbB /EGF receptor gene. Approximately one third of brain tumors of glial origin overexpress the EGF receptor and have amplification. Detailed analysis of genomic DNA from these tumors with various cDNA probes of the EGF receptor indicate that in addition to gene amplification the EGF receptor gene is rearranged. Hence, lesions in the gene of EGF receptor are associated with viral neoplasias in birds and also in human cancers. (J)

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA025820-08
Application #
3167031
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Project Start
1979-08-01
Project End
1988-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
8
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
Weizmann Institute of Science
Department
Type
DUNS #
City
Rehovot
State
Country
Israel
Zip Code
76100

  Publications

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Cochet, C; Kashles, O; Chambaz, E M et al. (1988) Demonstration of epidermal growth factor-induced receptor dimerization in living cells using a chemical covalent cross-linking agent. J Biol Chem 263:3290-5
Tal, M; Wetzler, M; Josefberg, Z et al. (1988) Sporadic amplification of the HER2/neu protooncogene in adenocarcinomas of various tissues. Cancer Res 48:1517-20
Schlessinger, J (1988) The epidermal growth factor receptor as a multifunctional allosteric protein. Biochemistry 27:3119-23
Livneh, E; Dull, T J; Berent, E et al. (1988) Release of a phorbol ester-induced mitogenic block by mutation at Thr-654 of the epidermal growth factor receptor. Mol Cell Biol 8:2302-8
Seger, R; Yarden, Y; Kashles, O et al. (1988) The epidermal growth factor receptor as a substrate for a kinase-splitting membranal proteinase. J Biol Chem 263:3496-500
Tal, M; King, C R; Kraus, M H et al. (1987) Human HER2 (neu) promoter: evidence for multiple mechanisms for transcriptional initiation. Mol Cell Biol 7:2597-601
Yarden, Y; Schlessinger, J (1987) Self-phosphorylation of epidermal growth factor receptor: evidence for a model of intermolecular allosteric activation. Biochemistry 26:1434-42
Yarden, Y; Schlessinger, J (1987) Epidermal growth factor induces rapid, reversible aggregation of the purified epidermal growth factor receptor. Biochemistry 26:1443-51
Popliker, M; Shatz, A; Avivi, A et al. (1987) Onset of endogenous synthesis of epidermal growth factor in neonatal mice. Dev Biol 119:38-44

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