Short form of the prolactin (PRL) receptor silences PRL induction of the beta-casein gene

The PRL receptor (PRLR) is a member of the cytokine receptor superfamily. Rats and mice express two forms of PRLR, short (SPRLR) and long (LPRLR), which differ in the length and sequence of their cytoplasmic domains, We have analyzed the ability of each form of rat PRLR to transduce lactogenic signals in a bovine mammary gland epithelial cell line, The rat PRLR forms were expressed and detected by RT-PCR, indirect immunofluorescence, and cell surface ligand binding, When the biological activity of each form of PRLR was assessed by transient transfection, we found that the long form was able to activate the beta-casein gene promoter and that the short form was inactive, Interestingly, the coexpression of both forms of PRLR resulted in a block of PRL signal to the milk protein gene promoter as a function of the concentration of the SPRLR. Similar results were obtained when LPRLR was coexpressed with totally or partially inactive tyrosine mutants of either the Nb2 form or the LPRLR form. Thus, these results suggest that the SPRLR form has at least one clear biological function, be. to silence lactogenic signals and to contribute to a differential and acute PRL effect in rat tissues. Furthermore, the data derived from coexpression of LPRLR and PRLR mutants confirm a crucial role of the C-terminal tyrosine residue in lactogenic signaling and the dimerization of PRLRs.