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.
O'Neal
K D
KD
Department of Microbiology and Immunology, Baylor College of Medicine, Houston, Texas 77030.
Yu-Lee
L Y
LY
D001483:Base Sequence; D002455:Cell Division; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D050856:Interferon Regulatory Factor-1; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D016185:Receptors, Interleukin-3 / Q000502:physiology; D011981:Receptors, Prolactin / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection
D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D010750:Phosphoproteins; D016185:Receptors, Interleukin-3; D011981:Receptors, Prolactin; D014157:Transcription Factors