title: Epidermal growth factor receptors.
abstract: EGF-Rs are cell membrane glycoproteins of wide distribution. They have not yet been fully characterized or purified but are probably molecules of 170-190,000 mol. wt. in most cells. The growth factor EGF binds and will saturate cell surface receptors with a KA of about 5 X 10(9) M-1 although a receptor class with an affinity in excess of 10(10) M-1 has been detected in some cells. The number of receptors on a cell does not determine the level of its response. Some cell types have receptors which bind EGF, but with no mitogenic response. The ways in which receptor affinity and/or number is modulated are described. This and other evidence is reviewed in a search for a suitable model of a mechanism of action on the cell, which best fits the current data. There is ample evidence that EGF binds to the receptor; that ligand-receptor complexes cluster or aggregate; and then are internalized and degraded, but evidence for a direct connection between internalization and the subsequent mitogenic response is lacking. Good correlations between internalization and mitogenic responses have been observed and developed into a theory of endocytic activation, but there is a body of evidence which cannot be accommodated by this theory. Instead, an alternative model is suggested.
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D004247:DNA / Q000096:biosynthesis; D004815:Epidermal Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D066246:ErbB Receptors; D005260:Female; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D008970:Molecular Weight; D009928:Organ Specificity; D010455:Peptides / Q000378:metabolism*; D011247:Pregnancy; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D013045:Species Specificity; D013724:Teratoma / Q000378:metabolism; D014018:Tissue Distribution; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D010455:Peptides; D011956:Receptors, Cell Surface; D014212:Tretinoin; D004815:Epidermal Growth Factor; D004247:DNA; D066246:ErbB Receptors