Functional heterogeneity of proto-oncogene tyrosine kinases

Journal Article · Sat Apr 01 04:00:00 EST 1989 · Molecular and Cellular Biology; (USA)

DOI:https://doi.org/10.1128/MCB.9.4.1772· OSTI ID:5719414

Velu, T J; Vass, W C; Lowy, D R ^[1]; Beguinot, L ^[2]

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1. National Cancer Inst., Bethesda, MD (USA)
2. Univ. Institute of Microbiology, Copenhagen (DK)

Previous reports have indicated that the C termini of the membrane-associated tyrosine kinases encoded by c-src and c-fms proto-oncogenes have a negative effect on their biological activity and that this effect is mediated by their C-terminal tyrosine residue. To determine whether this was true for the human epidermal growth factor (EGF) receptor, which is also a membrane-associated tyrosine kinase proto-oncogene, the authors have constructed two premature termination mutants, dc19 and dc63, that delete the C-terminal 19 and 63 amino acids, respectively, from the human full-length receptor (hEGFR). The smaller deletion removes the C-terminal tyrosine residue, while the larger deletion removes the two most C-terminal tyrosines; similar deletions are found in v-erbB. As previously shown for the gene encoding the full-length EGF receptor, the two C-terminal mutants induced EGF-dependent focal transformation and anchorage-independent growth of NIH 3T3 cells. However, both dc19 and dc63 were quantitatively less efficient than the gene encoding the full-length receptor, with dc63 being less active than dc19. Although the C-terminal mutants displayed lower biological activity than the gene encoding the full-length receptor, the mutant receptors were found to be similar in several respects to the full-length receptor. These parameters included receptor localization, stability in the absence of EGF, receptor half-life in the presence of EGF, EGF binding, extent of EGF-dependent autophosphorylation in vitro, and EGF-dependent phosphorylation of an exogenous substrate in vitro.

• OSTI ID: 5719414
• Journal Information: Molecular and Cellular Biology; (USA), Journal Name: Molecular and Cellular Biology; (USA) Vol. 9:4; ISSN MCEBD; ISSN 0270-7306
• Country of Publication: United States
• Language: English

Related Subjects

550200* -- Biochemistry
59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
BIOLOGICAL FUNCTIONS
BIOLOGICAL PATHWAYS
CARBOXYLIC ACIDS
CELL CONSTITUENTS
CELL MEMBRANES
CELL PROLIFERATION
CELL TRANSFORMATIONS
CHEMICAL REACTIONS
ENZYMES
FUNCTIONS
GENE REGULATION
GENES
GROWTH FACTORS
HYDROXY ACIDS
IN VITRO
MEMBRANE PROTEINS
MEMBRANES
MITOGENS
MOLECULAR BIOLOGY
ONCOGENES
ONCOGENIC TRANSFORMATIONS
ORGANIC ACIDS
ORGANIC COMPOUNDS
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHORYLATION
PHOSPHOTRANSFERASES
PROTEINS
RECEPTORS
TRANSFERASES
TYROSINE