Heterodimerization of the erbB-1 and erbB-2 receptors in human breast carcinoma cells: A mechanism for receptor transregulation

Journal Article · Sat Dec 01 04:00:00 EST 1990 · Biochemistry; (USA)

DOI:https://doi.org/10.1021/bi00502a002· OSTI ID:5674467

Goldman, R; Levy, R B; Peles, E; Yarden, Y ^[1]

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1. The Weizmann Institute of Science, Rehovot (Israel)

The erbB-1 and erbB-2 protooncogenes encode homologous membrane receptors that respectively bind epidermal growth factor (EGF) and a still incompletely characterized ligand. Binding of EFG to its receptor is known to increase tyrosine phosphorylation of the erbB-2/neu receptor in tumor cells. To investigate the mechanism of this transregulatory pathway, the authors analyzed the interactions between the two receptors in SKBR-3 human breast carcinoma cells. Chemical cross-linking of {sup 125}I-labeled EGF revealed that the radiolabeled EGF receptor coimmunoprecipitates with the erbB-2/neu receptor. In addition a cross-linked species of 360-kdalton molecular mass is also coimmunoprecipitated. The formation of the latter species of 360-kdalton molecular mass is also coimmunoprecipitated. The formation of the latter species is absolutely dependent on the presence of EGF receptor and thus appears to represent a heterodimer of the erbB-1 and erbB-2 receptors. In vitro kinase reaction assays revealed that receptor heterodimerization is induced by EGF binding and leads to a dramatic increase in the self-phosphorylation capacity of the dimerized receptors. Moreover, analysis of living SKBR-3 cells suggested that most of the EGF-induced transregulation of the erbB-2/neu receptor is due to receptor heterodimerization. In conclusion, heterodimers of erbB-1 and erbB-2 receptors may provide a mechanism for dual transductory functions of growth factors of breast tumor cells.

• OSTI ID: 5674467
• Journal Information: Biochemistry; (USA), Journal Name: Biochemistry; (USA) Vol. 29:50; ISSN 0006-2960; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
AUTORADIOGRAPHY
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CARCINOMAS
CHEMICAL REACTIONS
CROSS-LINKING
DAYS LIVING RADIOISOTOPES
DIMERIZATION
DISEASES
ELECTRON CAPTURE RADIOISOTOPES
GENE REGULATION
GENES
GROWTH FACTORS
INTERMEDIATE MASS NUCLEI
INTERNAL CONVERSION RADIOISOTOPES
IODINE 125
IODINE ISOTOPES
ISOTOPES
LIGHT NUCLEI
MEMBRANE PROTEINS
MITOGENS
NEOPLASMS
NUCLEI
ODD-EVEN NUCLEI
ODD-ODD NUCLEI
ONCOGENES
ORGANIC COMPOUNDS
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
POLYMERIZATION
PROTEINS
RADIOISOTOPES
RECEPTORS
TUMOR CELLS