Characterization of the mitogen regulated protein receptor

Nelson, Joseph
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Mitogen regulated protein (MRP) is a glycoprotein synthesized in murine placenta and secreted into the maternal bloodstream during gestation. The temporal profile of MRP concentration in the plasma during gestation, its synthesis in an organ known to secrete other lactogenic hormones, and its homology to prolactin suggest an hormonal role;A requisite characteristic of a polypeptide hormone is to have a receptor on the plasma membrane of another tissue separate from its site of synthesis. The receptor then mediates the functional effects by binding the hormone. I discovered and characterized a receptor for MRP from murine uterine membrane preparations. The MRP receptor exhibited differential binding characteristics during mid-gestation showing peak binding activity at 11 days of gestation. Maximal binding correlated with blood clearance as determined by radioisotope tracer studies. The receptor showed a single affinity for MRP with a dissociation constant of 3.2 x 10[superscript]-10 M and maximal binding of 72 fmoles of MRP per mg membrane protein at 11 days of gestation. Prolactin did not compete for binding with radioiodinated MRP at concentrations up to 45 nM. The MRP receptor had a molecular weight of about 23 KDa based on chemical crosslinking studies;MRP binds to the cation independent mannose-6-phosphate receptor in placental and liver membrane preparations during late gestation. Excess mannose-6-phosphate did not block MRP binding in uterine membrane preparations at mid-gestation;I conclude that MRP may be a hormone involved in fetal development and that the uterus is one target tissue of this hormone.

Biochemistry and biophysics, Biochemistry