Epidermal growth factor: uptake and fate.
Lateral diffusion of epidermal growth factor (EGF) receptors along the plane of the cell membrane can be measured using fluorescently labelled analogues of EGF and the fluorescence photobleaching recovery method in cultured cells. With the aid of high image-intensified fluorescent microscopy, the receptors, which are initially distributed diffusely, form patches and undergo endocytosis at 37 degrees C. These gross processes may not be critical in mediating the initial, rapid actions of the hormone. The processes of uptake and endocytosis correspond biochemically to the loss of surface receptors ('down-regulation') and degradation of the receptor and hormone via lysosomes. The EGF receptors are not apparently recycled or re-utilized, and they are continuously internalized, even in the absence of ligand. Since all manoeuvres that interfere with intracellular degradation or processing block mitogenesis, it is proposed that one or both of these may be essential processes, although in such a case they must be continuous and protracted functions. Slow nuclear accumulation of the complex of hormone and receptor may be an important process. In addition, evidence suggests that limited (submicroscopic) receptor aggregation (dimerization) at the cell surface may be necessary and sufficient to trigger the long-term effects (but not the immediate effects), and thus this aggregation may be required for endocytosis. The ligand itself may not be an essential structural component of the action of the receptor since anti-receptor antibodies can elicit mitogenic responses. Recent results suggest that EGF receptors normally exist in a low affinity state which is rapidly converted by EGF (at 37 degrees C but not at 4 degrees C) to a high affinity state by a process that requires prior intact protein synthesis. Furthermore, the accumulation of a special, stable intracellular pool of the complex may be related to the control of cellular growth (and tumour promotion).
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D004705:Endocytosis; D004815:Epidermal Growth Factor / Q000378:metabolism*; D066246:ErbB Receptors; D009414:Nerve Growth Factors / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*
D009414:Nerve Growth Factors; D011956:Receptors, Cell Surface; D004815:Epidermal Growth Factor; D066246:ErbB Receptors