Mutational analysis of a lactogenic hormone reveals a role for lactogen-specific amino acid residues in receptor binding and mitogenic activity.
Mutant forms of mouse placental lactogen-II (PL-II) have been generated to assess the role of specific amino acid residues and protein regions in binding to the PRL receptor and in mitogenic activity. Conversion of any of three lactogen-specific residues significantly reduced both of these hormone functions; mutation of the two other lactogen-specific amino acids revealed only minimal effects unless these changes were coupled with a second mutation. Deletions within the PL-II protein all resulted in a complete loss of function, but switching regions between PL-II and proliferin, another member of the prolactin family in the mouse, did yield a chimeric protein with some PRL-like activity. This activity was increased substantially by conversion of one amino acid residue in the proliferin region to the corresponding lactogen-specific residue. The locations of the amino acids that have been found to affect hormone function are predicted to be closely apposed in the folded protein, suggesting that this region may be the site of interaction of this lactogenic hormone with the PRL receptor.
Davis
J A
JA
Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois 60208.
Linzer
D I
DI
D000595:Amino Acid Sequence; D000818:Animals; D002678:Chimera; D051379:Mice; D008934:Mitogens / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D010928:Placental Lactogen / Q000235:genetics* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D018000:Receptors, Peptide
D008934:Mitogens; D011956:Receptors, Cell Surface; D018000:Receptors, Peptide; C028202:placental lactogen receptor; D010928:Placental Lactogen