Abstract
The prolactin (PRL) receptor is a member of the family of cytokine receptors that lack intrinsic tyrosine kinase activity but contain two conserved cysteines in their N-terminal regions and a WSXWS motif adjacent to their transmembrane domains. In a manner similar to the interferons (IFNs), exposure of cells to PRL results in tyrosine phosphorylation of several cellular proteins and the rapid transcriptional induction of the IFN regulatory factor 1 gene. In this communication, we demonstrate that treatment of rat Nb2 lymphoma cells with PRL activates a latent protein factor so that it binds to an enhancer in the IFN regulatory factor 1 gene. This enhancer has been shown to be required for IFN-gamma-activated expression of this gene. PRL-induced assembly of the DNA binding complex, PRL-stimulated factor, required tyrosine phosphorylation. PRL-stimulated factor contained at least one protein that was antigenically similar to the p91 transcription factor, a component of several transcription complexes required for cytokine-activated gene expression. PRL not only induced the tyrosine phosphorylation of p91 but also induced tyrosine phosphorylation of Jak2, a tyrosine kinase required for IFN-gamma-activated gene expression. These results provide evidence for a signaling mechanism, some of whose components are shared by both PRL and IFN-gamma receptors, that results in the expression of early response genes.
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Selected References
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- Argetsinger L. S., Campbell G. S., Yang X., Witthuhn B. A., Silvennoinen O., Ihle J. N., Carter-Su C. Identification of JAK2 as a growth hormone receptor-associated tyrosine kinase. Cell. 1993 Jul 30;74(2):237–244. doi: 10.1016/0092-8674(93)90415-m. [DOI] [PubMed] [Google Scholar]
- Bayat-Sarmadi M., Houdebine L. M. Effect of various protein kinase inhibitors on the induction of milk protein gene expression by prolactin. Mol Cell Endocrinol. 1993 Mar;92(1):127–134. doi: 10.1016/0303-7207(93)90083-v. [DOI] [PubMed] [Google Scholar]
- Bazan J. F. Structural design and molecular evolution of a cytokine receptor superfamily. Proc Natl Acad Sci U S A. 1990 Sep;87(18):6934–6938. doi: 10.1073/pnas.87.18.6934. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bonni A., Frank D. A., Schindler C., Greenberg M. E. Characterization of a pathway for ciliary neurotrophic factor signaling to the nucleus. Science. 1993 Dec 3;262(5139):1575–1579. doi: 10.1126/science.7504325. [DOI] [PubMed] [Google Scholar]
- David M., Romero G., Zhang Z. Y., Dixon J. E., Larner A. C. In vitro activation of the transcription factor ISGF3 by interferon alpha involves a membrane-associated tyrosine phosphatase and tyrosine kinase. J Biol Chem. 1993 Mar 25;268(9):6593–6599. [PubMed] [Google Scholar]
- Decker T., Lew D. J., Darnell J. E., Jr Two distinct alpha-interferon-dependent signal transduction pathways may contribute to activation of transcription of the guanylate-binding protein gene. Mol Cell Biol. 1991 Oct;11(10):5147–5153. doi: 10.1128/mcb.11.10.5147. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fan G., Carbajo P., Rillema J. A. Possible role of tyrosine kinases in the prolactin stimulation of cell division in Nb2 node lymphoma cells. Horm Metab Res. 1993 May;25(5):256–258. doi: 10.1055/s-2007-1002091. [DOI] [PubMed] [Google Scholar]
- Fu X. Y. A transcription factor with SH2 and SH3 domains is directly activated by an interferon alpha-induced cytoplasmic protein tyrosine kinase(s). Cell. 1992 Jul 24;70(2):323–335. doi: 10.1016/0092-8674(92)90106-m. [DOI] [PubMed] [Google Scholar]
- Fu X. Y., Kessler D. S., Veals S. A., Levy D. E., Darnell J. E., Jr ISGF3, the transcriptional activator induced by interferon alpha, consists of multiple interacting polypeptide chains. Proc Natl Acad Sci U S A. 1990 Nov;87(21):8555–8559. doi: 10.1073/pnas.87.21.8555. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fu X. Y., Zhang J. J. Transcription factor p91 interacts with the epidermal growth factor receptor and mediates activation of the c-fos gene promoter. Cell. 1993 Sep 24;74(6):1135–1145. doi: 10.1016/0092-8674(93)90734-8. [DOI] [PubMed] [Google Scholar]
- Guan K. L., Dixon J. E. Evidence for protein-tyrosine-phosphatase catalysis proceeding via a cysteine-phosphate intermediate. J Biol Chem. 1991 Sep 15;266(26):17026–17030. [PubMed] [Google Scholar]
- Igarashi K., David M., Finbloom D. S., Larner A. C. In vitro activation of the transcription factor gamma interferon activation factor by gamma interferon: evidence for a tyrosine phosphatase/kinase signaling cascade. Mol Cell Biol. 1993 Mar;13(3):1634–1640. doi: 10.1128/mcb.13.3.1634. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Igarashi K., David M., Larner A. C., Finbloom D. S. In vitro activation of a transcription factor by gamma interferon requires a membrane-associated tyrosine kinase and is mimicked by vanadate. Mol Cell Biol. 1993 Jul;13(7):3984–3989. doi: 10.1128/mcb.13.7.3984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kanno Y., Kozak C. A., Schindler C., Driggers P. H., Ennist D. L., Gleason S. L., Darnell J. E., Jr, Ozato K. The genomic structure of the murine ICSBP gene reveals the presence of the gamma interferon-responsive element, to which an ISGF3 alpha subunit (or similar) molecule binds. Mol Cell Biol. 1993 Jul;13(7):3951–3963. doi: 10.1128/mcb.13.7.3951. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kelly P. A., Djiane J., Postel-Vinay M. C., Edery M. The prolactin/growth hormone receptor family. Endocr Rev. 1991 Aug;12(3):235–251. doi: 10.1210/edrv-12-3-235. [DOI] [PubMed] [Google Scholar]
- Khan K. D., Shuai K., Lindwall G., Maher S. E., Darnell J. E., Jr, Bothwell A. L. Induction of the Ly-6A/E gene by interferon alpha/beta and gamma requires a DNA element to which a tyrosine-phosphorylated 91-kDa protein binds. Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6806–6810. doi: 10.1073/pnas.90.14.6806. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kotanides H., Reich N. C. Requirement of tyrosine phosphorylation for rapid activation of a DNA binding factor by IL-4. Science. 1993 Nov 19;262(5137):1265–1267. doi: 10.1126/science.7694370. [DOI] [PubMed] [Google Scholar]
- Larner A. C., David M., Feldman G. M., Igarashi K., Hackett R. H., Webb D. S., Sweitzer S. M., Petricoin E. F., 3rd, Finbloom D. S. Tyrosine phosphorylation of DNA binding proteins by multiple cytokines. Science. 1993 Sep 24;261(5129):1730–1733. doi: 10.1126/science.8378773. [DOI] [PubMed] [Google Scholar]
- Levy D., Darnell J. E., Jr Interferon-dependent transcriptional activation: signal transduction without second messenger involvement? New Biol. 1990 Oct;2(10):923–928. [PubMed] [Google Scholar]
- Lütticken C., Wegenka U. M., Yuan J., Buschmann J., Schindler C., Ziemiecki A., Harpur A. G., Wilks A. F., Yasukawa K., Taga T. Association of transcription factor APRF and protein kinase Jak1 with the interleukin-6 signal transducer gp130. Science. 1994 Jan 7;263(5143):89–92. doi: 10.1126/science.8272872. [DOI] [PubMed] [Google Scholar]
- Meyer D. J., Campbell G. S., Cochran B. H., Argetsinger L. S., Larner A. C., Finbloom D. S., Carter-Su C., Schwartz J. Growth hormone induces a DNA binding factor related to the interferon-stimulated 91-kDa transcription factor. J Biol Chem. 1994 Feb 18;269(7):4701–4704. [PubMed] [Google Scholar]
- Müller M., Briscoe J., Laxton C., Guschin D., Ziemiecki A., Silvennoinen O., Harpur A. G., Barbieri G., Witthuhn B. A., Schindler C. The protein tyrosine kinase JAK1 complements defects in interferon-alpha/beta and -gamma signal transduction. Nature. 1993 Nov 11;366(6451):129–135. doi: 10.1038/366129a0. [DOI] [PubMed] [Google Scholar]
- Pearse R. N., Feinman R., Ravetch J. V. Characterization of the promoter of the human gene encoding the high-affinity IgG receptor: transcriptional induction by gamma-interferon is mediated through common DNA response elements. Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11305–11309. doi: 10.1073/pnas.88.24.11305. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pearse R. N., Feinman R., Shuai K., Darnell J. E., Jr, Ravetch J. V. Interferon gamma-induced transcription of the high-affinity Fc receptor for IgG requires assembly of a complex that includes the 91-kDa subunit of transcription factor ISGF3. Proc Natl Acad Sci U S A. 1993 May 1;90(9):4314–4318. doi: 10.1073/pnas.90.9.4314. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Perez C., Wietzerbin J., Benech P. D. Two cis-DNA elements involved in myeloid-cell-specific expression and gamma interferon (IFN-gamma) activation of the human high-affinity Fc gamma receptor gene: a novel IFN regulatory mechanism. Mol Cell Biol. 1993 Apr;13(4):2182–2192. doi: 10.1128/mcb.13.4.2182. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Petricoin E. F., 3rd, Hackett R. H., Akai H., Igarashi K., Finbloom D. S., Larner A. C. Modulation of interferon signaling in human fibroblasts by phorbol esters. Mol Cell Biol. 1992 Oct;12(10):4486–4495. doi: 10.1128/mcb.12.10.4486. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rillema J. A., Campbell G. S., Lawson D. M., Carter-Su C. Evidence for a rapid stimulation of tyrosine kinase activity by prolactin in Nb2 rat lymphoma cells. Endocrinology. 1992 Aug;131(2):973–975. doi: 10.1210/endo.131.2.1639035. [DOI] [PubMed] [Google Scholar]
- Ruff-Jamison S., Chen K., Cohen S. Induction by EGF and interferon-gamma of tyrosine phosphorylated DNA binding proteins in mouse liver nuclei. Science. 1993 Sep 24;261(5129):1733–1736. doi: 10.1126/science.8378774. [DOI] [PubMed] [Google Scholar]
- Rui H., Djeu J. Y., Evans G. A., Kelly P. A., Farrar W. L. Prolactin receptor triggering. Evidence for rapid tyrosine kinase activation. J Biol Chem. 1992 Nov 25;267(33):24076–24081. [PubMed] [Google Scholar]
- Sadowski H. B., Shuai K., Darnell J. E., Jr, Gilman M. Z. A common nuclear signal transduction pathway activated by growth factor and cytokine receptors. Science. 1993 Sep 24;261(5129):1739–1744. doi: 10.1126/science.8397445. [DOI] [PubMed] [Google Scholar]
- Schindler C., Fu X. Y., Improta T., Aebersold R., Darnell J. E., Jr Proteins of transcription factor ISGF-3: one gene encodes the 91-and 84-kDa ISGF-3 proteins that are activated by interferon alpha. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7836–7839. doi: 10.1073/pnas.89.16.7836. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schindler C., Shuai K., Prezioso V. R., Darnell J. E., Jr Interferon-dependent tyrosine phosphorylation of a latent cytoplasmic transcription factor. Science. 1992 Aug 7;257(5071):809–813. doi: 10.1126/science.1496401. [DOI] [PubMed] [Google Scholar]
- Shuai K., Schindler C., Prezioso V. R., Darnell J. E., Jr Activation of transcription by IFN-gamma: tyrosine phosphorylation of a 91-kD DNA binding protein. Science. 1992 Dec 11;258(5089):1808–1812. doi: 10.1126/science.1281555. [DOI] [PubMed] [Google Scholar]
- Shuai K., Schindler C., Prezioso V. R., Darnell J. E., Jr Activation of transcription by IFN-gamma: tyrosine phosphorylation of a 91-kD DNA binding protein. Science. 1992 Dec 11;258(5089):1808–1812. doi: 10.1126/science.1281555. [DOI] [PubMed] [Google Scholar]
- Shuai K., Ziemiecki A., Wilks A. F., Harpur A. G., Sadowski H. B., Gilman M. Z., Darnell J. E. Polypeptide signalling to the nucleus through tyrosine phosphorylation of Jak and Stat proteins. Nature. 1993 Dec 9;366(6455):580–583. doi: 10.1038/366580a0. [DOI] [PubMed] [Google Scholar]
- Silvennoinen O., Ihle J. N., Schlessinger J., Levy D. E. Interferon-induced nuclear signalling by Jak protein tyrosine kinases. Nature. 1993 Dec 9;366(6455):583–585. doi: 10.1038/366583a0. [DOI] [PubMed] [Google Scholar]
- Silvennoinen O., Witthuhn B. A., Quelle F. W., Cleveland J. L., Yi T., Ihle J. N. Structure of the murine Jak2 protein-tyrosine kinase and its role in interleukin 3 signal transduction. Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8429–8433. doi: 10.1073/pnas.90.18.8429. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sims S. H., Cha Y., Romine M. F., Gao P. Q., Gottlieb K., Deisseroth A. B. A novel interferon-inducible domain: structural and functional analysis of the human interferon regulatory factor 1 gene promoter. Mol Cell Biol. 1993 Jan;13(1):690–702. doi: 10.1128/mcb.13.1.690. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stahl N., Boulton T. G., Farruggella T., Ip N. Y., Davis S., Witthuhn B. A., Quelle F. W., Silvennoinen O., Barbieri G., Pellegrini S. Association and activation of Jak-Tyk kinases by CNTF-LIF-OSM-IL-6 beta receptor components. Science. 1994 Jan 7;263(5143):92–95. doi: 10.1126/science.8272873. [DOI] [PubMed] [Google Scholar]
- Velazquez L., Fellous M., Stark G. R., Pellegrini S. A protein tyrosine kinase in the interferon alpha/beta signaling pathway. Cell. 1992 Jul 24;70(2):313–322. doi: 10.1016/0092-8674(92)90105-l. [DOI] [PubMed] [Google Scholar]
- Watling D., Guschin D., Müller M., Silvennoinen O., Witthuhn B. A., Quelle F. W., Rogers N. C., Schindler C., Stark G. R., Ihle J. N. Complementation by the protein tyrosine kinase JAK2 of a mutant cell line defective in the interferon-gamma signal transduction pathway. Nature. 1993 Nov 11;366(6451):166–170. doi: 10.1038/366166a0. [DOI] [PubMed] [Google Scholar]
- Witthuhn B. A., Quelle F. W., Silvennoinen O., Yi T., Tang B., Miura O., Ihle J. N. JAK2 associates with the erythropoietin receptor and is tyrosine phosphorylated and activated following stimulation with erythropoietin. Cell. 1993 Jul 30;74(2):227–236. doi: 10.1016/0092-8674(93)90414-l. [DOI] [PubMed] [Google Scholar]
- Yu-Lee L. Y., Hrachovy J. A., Stevens A. M., Schwarz L. A. Interferon-regulatory factor 1 is an immediate-early gene under transcriptional regulation by prolactin in Nb2 T cells. Mol Cell Biol. 1990 Jun;10(6):3087–3094. doi: 10.1128/mcb.10.6.3087. [DOI] [PMC free article] [PubMed] [Google Scholar]