Epidermal growth factor cell membrane binding

Another TIR/FRAP study on biological cell membranes has examined the reversible but specific binding kinetics of fluorescence-labeled epidermal growth factor to the surface of cells.(125) The background problem here was solved simply by choosing cells with a very large concentration of epidermal... 

A group of receptors exists that responds to so-called growth factors such as insulin, epidermal growth factor, platelet-derived growth factor, etc. These receptors have an extracellular domain that binds the growth factor and an intracellular domain that possesses latent kinase activity. The interaction of insulin, for example, results in autophosphorylation of the intracellular domain and subsequent internalization of the insulin-receptor complex. The internalized complex now possesses the properties of a tyrosine kinase and can phosphorylate cell substrates that produce the appropriate intracellular effect. However, these kinases differ from the usual protein kinases in that they phosphorylate proteins exclusively on tyrosine hydroxyl residues. The ensemble of proteins phosphorylated by the insulin receptor has not yet been identified, but there is supportive evidence that tyrosine kinase activity is required for the major actions of insulin. For example, it is possible that a membrane-linked glucose transport system becomes activated following insulin-stimulated phosphorylation. 

Fig. 6-24 Schematic representation of the epidermal growth factor (EGF) receptor. The receptor is an integral membrane protein with a single transmembrane domain. The ligand binding site is in the extracellular domain and there is a tyrosine kinase domain near the C terminus in the cytoplasm, (a) At rest the receptor exists as single subunits. (b) Upon binding EGF, the receptor forms dimers stabilized by noncovalent associations. After dimerization the activated tyrosine kinase phosphorylates tyrosine residues in the cytoplasmic domain prior to the recruitment of further proteins to bind to the receptor. The formation of a protein assembly on the cytoplasmic domain is necessary for activation of enzymes that regulate cell metabolism and gene transcription.

Anklesatia, P., Teixido, J., Marikki, L., Pierce, J. H. and Greenberger, J. S. (1990). Cell-cell adhesion mediated by binding of membrane- anchored transforming groath factor alpha to epidermal growth factor receptors promotes cell proliferation. Proc. Natl. Acad. Sci. USA 87, 3289-3293. 

EGF-active factors (76), that are structurally similar to poly-APS, prevent binding of epidermal growth factors to their receptors on cell membranes, resulting in decreased DNA synthesis and cell proliferation. These compounds also bind to insulin receptors, albeit with about 10 fold lesser affinity [33]. 

Fig. 5.6 Fluorescence microscopy illustrating binding of fluorescein-conjugated human epidermal growth factor (hEGF) to the cell membrane of a single MDA-MB-458 human breast cancer cell, followed by internalization into cytoplasmic vesicles,...

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