Binding of epidermal growth factor to its receptor is affected by membrane phospholipid environment.
Cells of epithelial origin generally require ethanolamine to grow in culture; when these cells are grown without ethanolamine, the phosphatidylethanolamine content of their membrane phospholipid becomes 1/2 to 1/3 of the normal amount, and growth stops. We have hypothesized that growth ceases because the phospholipid environment becomes unsuitable for membrane-associated function. Using ethanolamine-requiring rat mammary cells, we have investigated the possible effect of phosphatidylethanolamine deficiency on the binding characteristics of epidermal growth factor. Apparent dissociation constant for the high-affinity sites in cells having normal membrane phospholipid was 1.7 X 10(-10) M, whereas that of phosphatidylethanolamine-deficient cells was 2.7 X 10(-10) M: the difference was small, but significant. Pretreatment with phorbol ester caused the loss of high-affinity sites in cells having normal membrane, whereas binding characteristics of epidermal growth factor became refractory to the pretreatment in phosphatidylethanolamine-deficient cells. In addition, the rate of internalization of bound epidermal growth factor in phosphatidylethanolamine-deficient cells was about 1/4 of normal cells. Further, whether cells had normal or phosphatidylethanolamine-deficient membranes seemed to affect the phosphorylation patterns of membrane proteins in response to epidermal growth factor or phorbol ester. These results suggest that membrane phospholipid environment affects the activity of the epidermal growth factor receptor.
Kano-Sueoka
T
T
Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder 80309-0347.
King
D M
DM
Fisk
H A
HA
Klug
S J
SJ
D000818:Animals; D002455:Cell Division; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology; D004815:Epidermal Growth Factor / Q000378:metabolism*; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D066246:ErbB Receptors / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008325:Mammary Neoplasms, Experimental; D008563:Membrane Lipids / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010714:Phosphatidylethanolamines / Q000172:deficiency; D010743:Phospholipids / Q000502:physiology*; D010766:Phosphorylation; D051381:Rats
D008563:Membrane Lipids; D008565:Membrane Proteins; D010714:Phosphatidylethanolamines; D010743:Phospholipids; D015240:Phorbol 12,13-Dibutyrate; D004815:Epidermal Growth Factor; D066246:ErbB Receptors