Regulation of the production of a prolactin-like protein (MRP/PLF) in 3T3 cells and in the mouse placenta.
Mitogen-regulated protein (MRP), a heterogeneously glycosylated mouse protein of Mr 34,000, is in the same protein family as prolactin, growth hormone, and placental lactogen. We show here that the level of translatable MRP mRNA is increased in response to fibroblast growth factor. Also, the amount of MRP secreted by 3T3 cells is modulated by the rate of degradation of newly synthesized MRP in the lysosomes. This is indicated by several results. First, agents that inhibit protein degradation by lysosomal proteases selectively increased by 2- to 6-fold the incorporation of [35S]methionine into MRP. These agents are ammonium chloride, the carboxylic ionophores, monensin and nigericin, and two thiol protease inhibitors, leupeptin and antipain. MRP that has already been secreted is not degraded by 3T3 cells. We examined the developmental appearance of MRP using immunofluorescence microscopy and found MRP localized in the mouse placenta between days 9 and 13 of development. The amount of MRP in the placenta drops suddenly after day 13. Whereas the appearance of MRP in the placenta follows the reported appearance of its mRNA, MRP disappears from the placenta more rapidly than its mRNA. On the basis of the results of our studies with cells in culture we propose that the production of MRP in the placenta is regulated similarly to prolactin. Thus we propose that the initial increase in MRP production in the placenta is due to pretranslational regulation by growth factors, and the later rapid decline is due to posttranslational regulation through degradation in the lysosomes.
Nilsen-Hamilton
M
M
Department of Biochemistry and Biophysics, Iowa State University, Ames 50011.
Jang
Y J
YJ
Alvarez-Azaustre
E
E
Hamilton
R T
RT
D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D000976:Antipain / Q000494:pharmacology; D002460:Cell Line; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D006023:Glycoproteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D006031:Glycosylation; D036341:Intercellular Signaling Peptides and Proteins; D007700:Kinetics; D007976:Leupeptins / Q000494:pharmacology; D051379:Mice; D008985:Monensin / Q000494:pharmacology; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011388:Prolactin; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D007976:Leupeptins; C000634106:Prl2c2 protein, mouse; D012333:RNA, Messenger; D000643:Ammonium Chloride; D000976:Antipain; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor; D011388:Prolactin; D008985:Monensin; C032854:leupeptin