Molecular Cloning and Expression of an Additional Epidermal Growth Factor Receptor-Related Gene

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 87; no. 13; pp. 4905 - 4909
• Main Authors: Plowman, Gregory D., Whitney, Gena S., Neubauer, Michael G., Green, Janell M., McDonald, Vicki L., Todaro, George J., Shoyab, Mohammed
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01-07-1990; National Acad Sciences
• Subjects: 550201 - Biochemistry- Tracer Techniques; AMINO ACID SEQUENCE; AMINO ACIDS; amphiregulin; ANIMAL CELLS; ANIMALS; Base Sequence; BASIC BIOLOGICAL SCIENCES; Biochemistry; Biological and medical sciences; CARBOXYLIC ACIDS; CARCINOMAS; Cell growth; Cell Line; Cell lines; Cell receptors; Cell structures and functions; CLONING; Cloning, Molecular - methods; Complementary DNA; COS cells; DISEASES; DNA; DNA HYBRIDIZATION; DNA-CLONING; ENZYMES; epidermal growth factor; ErbB Receptors - genetics; Fundamental and applied biological sciences. Psychology; Gene Expression; GENES; GROWTH FACTORS; Hormone receptors. Growth factor receptors. Cytokine receptors. Prostaglandin receptors; Humans; HYBRIDIZATION; HYDROXY ACIDS; Ligands; MAMMALS; MAN; MEMBRANE PROTEINS; MITOGENS; Molecular and cellular biology; Molecular Sequence Data; MOLECULAR STRUCTURE; NEOPLASMS; NUCLEIC ACIDS; Oligonucleotide Probes; ORGANIC ACIDS; ORGANIC COMPOUNDS; PHOSPHORUS-GROUP TRANSFERASES; PHOSPHOTRANSFERASES; Polymerase chain reaction; PRIMATES; Protein Conformation; Protein-Tyrosine Kinases - genetics; PROTEINS; RECEPTORS; RECOMBINANT DNA; RNA; Sequence Homology, Nucleic Acid; TRANSCRIPTION; Transfection; TRANSFERASES; TUMOR CELLS; Tumor Cells, Cultured - enzymology; TYROSINE; VERTEBRATES; Human; Membrane receptor; Nucleotide sequence; Tumor; Molecular cloning; Gene expression; Growth factor
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.87.13.4905

Epidermal growth factor (EGF), transforming growth factor α (TGF-α), and amphiregulin are structurally and functionally related growth regulatory proteins. These secreted polypeptides all bind to the 170-kDa cell-surface EGF receptor, activating its intrinsic kinase activity. However, amphiregulin exhibits different activities than EGF and TGF-α in a number of biological assays. Amphiregulin only partially competes with EGF for binding EGF receptor, and amphiregulin does not induce anchorage-independent growth of normal rat kidney cells (NRK) in the presence of TGF-β. Amphiregulin also appears to abrogate the stimulatory effect of TGF-α on the growth of several aggressive epithelial carcinomas that over-express EGF receptor. These findings suggest that amphiregulin may interact with a separate receptor in certain cell types. Here we report the cloning of another member of the human EGF receptor (HER) family of receptor tyrosine kinases, which we have named "HER3/ERRB3." The cDNA was isolated from a human carcinoma cell line, and its 6-kilobase transcript was identified in various human tissues. We have generated peptide-specific antisera that recognizes the 160-kDa HER3 protein when transiently expressed in COS cells. These reagents will allow us to determine whether HER3 binds amphiregulin or other growth regulatory proteins and what role HER3 protein plays in the regulation of cell growth.