A mutant lactogenic hormone binds, but does not activate, the prolactin receptor.
We have generated mutations in mouse placental lactogen II, a hormone in the PRL/GH family that binds to the PRL receptor, to investigate the role of the conserved cysteine residues in hormone function. Disruption of the small C-terminal disulfide loop did not significantly alter hormone activity. Substitution of serine for cysteine-51, which prevents formation of the large disulfide loop, results in a protein equivalent to placental lactogen II in receptor-binding activity; however, this mutant protein is not mitogenic in an assay for lactogenic hormones. These results indicate that PRL receptor occupancy and activation are distinct events.
Davis
J A
JA
Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois 60208.
Linzer
D I
DI
D000818:Animals; D051379:Mice; D009154:Mutation; D010928:Placental Lactogen / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D011981:Receptors, Prolactin / Q000187:drug effects / Q000378:metabolism*
D011981:Receptors, Prolactin; D010928:Placental Lactogen