Differential signal transduction of the short, Nb2, and long prolactin receptors. Activation of interferon regulatory factor-1 and cell proliferation.

An Nb2 prolactin receptor (PRL-R) cDNA has been cloned from the PRL-dependent 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-Sp. Short, Nb2, and long forms of the PRL-R were analyzed for signal transduction to the immediate-early gene, interferon regulatory factor-1 (IRF-1) and for cellular proliferation. Receptor and IRF-1-CAT reporter constructs were transiently cotransfected into the interleukin-3-dependent 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 promoter. Stable transfectants were also generated by selecting for growth in PRL. Only the Nb2 and long forms were able to convert the IL-3-dependent cells to PRL-dependence. IRF-1-CAT was induced in these cell lines by the Nb2 PRL-R 10- to 12-fold and long PRL-R 3- to 3.5-fold. Overall, the Nb2 form is more efficient than the long form by about 3-fold 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 the long form. A PRL dose-response for IRF-1-CAT activity gave similar results, indicating a tight correlation between IRF-1 induction and cell proliferation. These results show that the short PRL-R does not signal to IRF-1 or for growth, and that the Nb2 PRL-R signals more efficiently than the long PRL-R.