Related Experiment Videos
A mutant lactogenic hormone binds, but does not activate, the prolactin receptor
1Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois 60208.
Molecular Endocrinology (Baltimore, Md.)
|June 1, 1989
Summary
Mutations in mouse placental lactogen II reveal that while receptor binding is unaffected, a key disulfide loop is essential for mitogenic activity, distinguishing hormone binding from receptor activation. This finding clarifies hormone signaling mechanisms.
Area of Science:
- Endocrinology
- Molecular Biology
- Hormone Signaling
Background:
- Mouse placental lactogen II (PL II) is a hormone in the prolactin/growth hormone (PRL/GH) family.
- PL II interacts with the prolactin receptor (PRL receptor).
- Conserved cysteine residues are critical for the structure and function of many protein hormones.
Purpose of the Study:
- To investigate the role of conserved cysteine residues in mouse placental lactogen II function.
- To determine how specific disulfide loops affect hormone activity and receptor interaction.
Main Methods:
- Site-directed mutagenesis was used to generate mutations in mouse placental lactogen II.
- Mutant proteins were assessed for receptor-binding activity.
- Mitogenic activity of mutant proteins was evaluated using a lactogenic hormone assay.
Main Results:
- Disrupting the small C-terminal disulfide loop did not significantly alter hormone activity.
- Substituting serine for cysteine-51, preventing the large disulfide loop, yielded a mutant protein with equivalent receptor-binding activity to wild-type PL II.
- This Cys-51 mutant protein lacked mitogenic activity in the lactogenic hormone assay.
Conclusions:
- PRL receptor occupancy and receptor activation are distinct events.
- The large disulfide loop in placental lactogen II is crucial for mitogenic signaling, not just receptor binding.
- These findings provide insights into the structure-function relationships of PRL/GH family hormones.