Effects of epidermal growth factor (EGF) and prolactin on EGF receptor cytoskeletal association in mammary epithelial cells.
Prolactin treatment of NMuMG mammary epithelial cells inhibits the ability of epidermal growth factor (EGF) to transduce a variety of signals, possibly by interfering with receptor tyrosine phosphorylation. However, the mechanism by which prolactin inhibits EGF receptor signaling is unclear. The objective of this study was to evaluate the effects of prolactin on the dynamics of EGF receptor degradation and resynthesis, and on the association of the receptor with the cytoskeleton. EGF decreased the EGF receptor content of NMuMG cells, and this decrease was unaffected by prolactin treatment. Subsequent to the decrease in EGF receptors, cells reaccumulated EGF receptors, and this re-accumulation was also unaffected by prolactin. In other studies, EGF induced a rapid association of EGF receptor with Triton X-100-insoluble (cytoskeletal) elements. The cytoskeletally associated receptors were more heavily tyrosine phosphorylated than soluble receptors in the absence of prolactin. In the presence of prolactin, similar amounts of EGF receptor associated with the cytoskeleton, but both cytoskeletal and soluble receptors exhibited decreased tyrosine phosphorylation. These studies indicate that the effects of prolactin on EGF receptor signaling are not likely to be due to altered receptor dynamics or cytoskeletal association but are more likely due to an alteration in receptor kinase activity.
Prusheik
K
K
Endocrinology-Reproductive Physiology Program, University of Wisconsin, Madison 53706, USA.
Ladd
A N
AN
Sheffield
L G
LG
D000818:Animals; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D004338:Drug Combinations; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D004848:Epithelium / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D008321:Mammary Glands, Animal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D011388:Prolactin / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism
D004338:Drug Combinations; D004815:Epidermal Growth Factor; D011388:Prolactin; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases