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Dissociation of cellular responses to epidermal growth factor using anti‐receptor monoclonal antibodies.
Author(s) -
Defize L.H.,
Moolenaar W.H.,
Saag P.T.,
Laat S.W.
Publication year - 1986
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1986.tb04345.x
Subject(s) - biology , monoclonal antibody , epidermal growth factor receptor , antibody , receptor , epidermal growth factor , microbiology and biotechnology , virology , immunology , biochemistry
Three biologically active monoclonal antibodies against the human epidermal growth factor (EGF) receptor (2E9, 2D11 and 2G5) have been used to analyse the interrelationship between various cellular responses to EGF. Antibody 2E9 (IgG1) is directed against the protein core of the receptor, close to or at the EGF binding site, while 2D11 (IgG3) and 2G5 (IgG2a) recognize blood‐group A‐related carbohydrate determinants of the receptor. These antibodies have EGF‐like effects in that they can activate the receptor tyrosine kinase both in vitro and in vivo. Cross‐linking of the receptor‐bound antibodies by a second antibody mimics EGF in inducing a rapid aggregation of receptors on the cell surface. However, all three antibodies fail to mimic EGF in raising cytoplasmic pH and free Ca2+ and do not stimulate DNA synthesis in quiescent fibroblasts, even after external cross‐linking of the occupied receptors. It is concluded that EGF‐R tyrosine kinase activity as well as substrate specificity can be modulated by ligands other than EGF, even if they bind to sites distinct from the EGF binding domain; activation of the receptor tyrosine kinase, receptor clustering and induction of the ionic signals are causally unrelated events; and tyrosine kinase activation and receptor cross‐linking are not sufficient for stimulation of DNA synthesis.