DIFFERENTIAL SIGNAL-TRANSDUCTION OF THE SHORT, NB2, AND LONG PROLACTIN RECEPTORS - ACTIVATION OF INTERFERON REGULATORY FACTOR-I AND CELL-PROLIFERATION

An Nb2 prolactin receptor (PRL-R) cDNA has been cloned from the PRL-de pendent Nb2-11C cell line, and the protein-coding region is identical to that of the PRL-R isolated from the PRL-independent cell line Nb2-S p. Short, Nb2, and long forms of the PRL-R were analyzed for signal tr ansduction to the immediate-early gene, interferon regulatory factor-1 (IRF-1) and for cellular proliferation. Receptor and IRF-1-CAT report er constructs were transiently cotransfected into the interleukin-3 de pendent cell lines FDC-P1 and BaF3. The Nb2 PRL-R induced IRF-1-CAT 14 .3-fold on addition of PRL, while the long PRL-R induced IRF-1-CAT 5.6 -fold in FDC-P1 cells. The short PRL-R did not activate the IRF-1 prom oter. Stable transfectants were also generated by selecting for growth in PRL. Only the Nb2 and long forms were able to convert the IL-3-dep endent cells to PRL-dependence. IRF-1-CAT was induced in these cell li nes by the Nb2 PRL-R 10- to 12-fold and long PRL-R 3- to 3.5-fold. Ove rall, the Nb2 form is more efficient than the long form by about 3-fol d at inducing IRF-1-CAT. A PRL dose-response growth curve showed that the Nb2 form requires 20-fold less PRL for half maximal growth than th e long form. A PRL dose-response for IRF-1-CAT activity gave similar r esults, indicating a tight correlation between IRF-1 induction and cel l proliferation. These results show that the short PRL-R does not sign al to IRF-1 or for growth, and that the Nb2 PRL-R signals more efficie ntly than the long PRL-R.