Molecular bases of the interaction between human prolactin and its membrane receptor: A ten year study

In this review, we make a chronologically overview of a project aimed at deciphering the molecular bases of the mechanism by which prolactin, a pituitary-secreted polypeptidic hormone, interacts with its membrane receptor, a member of the cytokine receptor superfamily. This study, based essentially on structural and mutational analysis of human prolactin, has identified two regions interacting with the receptor, named binding sites 1 and 2. We have also provided evidence that prolactin induces dimerization of its receptor through its two binding sites, and based on that mechanism of activation, we have engineered and characterized prolactin antagonists able to block the effect of the hormone by competition for receptor binding. Our study has also highlighted the importance of using well characterized bioassays to monitor such a structure-function study since the properties of a given hormone analog were shown to strongly differ depending on the bioassay used.