Abstract
Proliferin is a prolactin-related glycoprotein secreted by proliferating mouse cell lines and by mouse placenta. In an attempt to identify target sites for proliferin action, we looked for proliferin receptors in murine fetal and maternal tissues during pregnancy using proliferin purified from the conditioned medium of a constructed Chinese hamster ovary cell line carrying amplified copies of proliferin cDNA. Purified proliferin bound to membrane preparations from fetal or maternal liver and from placenta with a Kd of 1 to 2 nM. The amount of proliferin bound per microgram of membrane protein varied markedly during pregnancy; maximal binding to day 16 fetal liver membranes was approximately 25 times that to liver membranes from adult animals. Binding to fetal and maternal receptors was specifically and completely inhibited by mannose 6-phosphate, with half-maximal inhibition at 10 microM. Furthermore, non-glycosylated proliferin did not inhibit the binding of the glycosylated protein. A approximately 300 Kd proliferin receptor was purified from the liver of pregnant mice using a proliferin affinity column and elution with mannose 6-phosphate. This receptor reacted with antibodies directed against the rat cation-independent mannose 6-phosphate receptor. We conclude that 1) proliferin secreted by cultured cell binds to cation-independent mannose 6-phosphate receptors and therefore may be a lysosomal protein or targeted to lysosomes, and 2) the concentration or activity of mannose 6-phosphate receptors in murine fetal and maternal liver and in placenta is regulated during pregnancy.
Highlights
From the Howard HughesMedical Institute Laboratory and the Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland21205
In anattempttoidentifytargetsitesfor the hypothesis that proliferin maybe an autocrine growth proliferin action,we looked for proliferin receptors in factor for cells incultureanda placental hormone that murine fetal and maternal tissues during pregnancy regulates growth and/or differentiation of specific cells in the using proliferin purified from thcoenditioned medium mouse fetus or in maternal tissues
The amount of proliferin bound per microgram of membrane protein varied markedly during pregnancy; maximal binding to day 16 fetal liver membranes was approximately26 times that to livemr empectedly, we found that proliferin secreted by cultured cell lines binds to the cation-independent mannose 6-phosphate receptor present in membranes from both fetal and maternal tissues and that theconcentration or activity of these receptors changes markedly during pregnancy
Summary
This receptor was immunoprecipitated with antibodies directed against thecation-independenrt eceptorprepared from rat liver (Brown and Farquhar,1984) (Fig. 14). These data1)indicate that the proliferin receptor detected in the liver of pregnant mice and in fetalliver is probably the high molecular weight (cation-independent) mannose 6-phosphatereceptor characterized previously, and 2) confirm that the amount of active receptor changes duringpregnancy
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