Design of Conditionally Active STATs: Insights into STAT Activation and Gene Regulatory Function
Open accessAbstract
The STAT (signal transducer and activator of transcription) signaling pathway is activated by a large number of cytokines and growth factors. We sought to design a conditionally active STAT that could not only provide insight into basic questions about STAT function but also serve as a powerful tool to determine the precise biological role of STATs. To this end, we have developed a conditionally active STAT by fusing STATs with the ligand-binding domain of the estrogen receptor (ER). We have demonstrated that the resulting STAT-ER chimeras are estrogen-inducible transcription factors that retain the functional and biochemical characteristics of the cognate wild-type STATs. In addition, these tools have allowed us to evaluate separately the contribution of tyrosine phosphorylation and dimerization to STAT function. We have for the first time provided experimental data supporting the model that the only apparent role of STAT tyrosine phosphorylation is to drive dimerization, as dimerization alone is sufficient to unmask a latent STAT nuclear localization sequence and induce nuclear translocation, sequence-specific DNA binding, and transcriptional activity.
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Dimerization is sufficient for nuclear import of activated Stat1.
“This observation extends the previous finding that dimerization is sufficient for nuclear import of activated Stat1 (Milocco et al. 1999).”
From DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 (2003) · cites this paper as Milocco et al. 1999
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Research works printed but not linked: 72
- [1]Ali S, Ali S. Prolactin receptor regulates Stat5 tyrosine phosphorylation and nuclear translocation by two separate pathways. J Biol Chem. 1998;273:7709–7716. doi: 10.1074/jbc.273.13.7709. [DOI] [PubMed] [Google Scholar] · DOI
- [2]Bach E A, Aguet M, Schreiber R D. The IFN gamma receptor: a paradigm for cytokine receptor signaling. Annu Rev Immunol. 1997;15:563–591. doi: 10.1146/annurev.immunol.15.1.563. [DOI] [PubMed] [Google Scholar] · DOI
- [3]Becker S, Groner B, Muller C W. Three-dimensional structure of the Stat3beta homodimer bound to DNA. Nature. 1998;394:145–151. doi: 10.1038/28101. [DOI] [PubMed] [Google Scholar] · DOI
- [4]Berry M, Metzger D, Chambon P. Role of the two activating domains of the oestrogen receptor in the cell-type and promoter-context dependent agonistic activity of the anti-oestrogen 4-hydroxytamoxifen. EMBO J. 1990;9:2811–2818. doi: 10.1002/j.1460-2075.1990.tb07469.x. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- [5]Bromberg J F, Horvath C M, Besser D, Lathem W W, Darnell J E., Jr Stat3 activation is required for cellular transformation by v-src. Mol Cell Biol. 1998;18:2553–2558. doi: 10.1128/mcb.18.5.2553. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI · Paper page
- [6]Carlesso N, Frank D A, Griffin J D. Tyrosyl phosphorylation and DNA binding activity of signal transducers and activators of transcription (STAT) proteins in hematopoietic cell lines transformed by Bcr/Abl. J Exp Med. 1996;183:811–820. doi: 10.1084/jem.183.3.811. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- [7]Chen X, Vinkemeier U, Zhao Y, Jeruzalmi D, Darnell J E, Jr, Kuriyan J. Crystal structure of a tyrosine phosphorylated STAT-1 dimer bound to DNA. Cell. 1998;93:827–839. doi: 10.1016/s0092-8674(00)81443-9. [DOI] [PubMed] [Google Scholar] · DOI
- [8]Chin H, Nakamura N, Kamiyama R, Miyasaka N, Ihle J N, Miura O. Physical and functional interactions between Stat5 and the tyrosine-phosphorylated receptors for erythropoietin and interleukin-3. Blood. 1996;88:4415–4425. [PubMed] [Google Scholar]
- [9]Chretien S, Varlet P, Verdier F, Gobert S, Cartron J P, Gisselbrecht S, Mayeux P, Lacombe C. Erythropoietin-induced erythroid differentiation of the human erythroleukemia cell line TF-1 correlates with impaired STAT5 activation. EMBO J. 1996;15:4174–4181. [PMC free article] [PubMed] [Google Scholar]
- [10]Danielian P S, White R, Hoare S A, Fawell S E, Parker M G. Identification of residues in the estrogen receptor that confer differential sensitivity to estrogen and hydroxytamoxifen. Mol Endocrinol. 1993;7:232–240. doi: 10.1210/mend.7.2.8469236. [DOI] [PubMed] [Google Scholar] · DOI
- [11]Darnell J E., Jr STATs and gene regulation. Science. 1997;277:1630–1635. doi: 10.1126/science.277.5332.1630. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
- [12]Delphin S, Stavnezer J. Characterization of an interleukin 4 (IL-4) responsive region in the immunoglobulin heavy chain germline epsilon promoter: regulation by NF- IL-4, a C/EBP family member and NF-kappa B/p50. J Exp Med. 1995;181:181–192. doi: 10.1084/jem.181.1.181. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- [13]Drachman J G, Kaushansky K. Dissecting the thrombopoietin receptor: functional elements of the Mpl cytoplasmic domain. Proc Natl Acad Sci USA. 1997;94:2350–2355. doi: 10.1073/pnas.94.6.2350. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI · Paper page
- [14]Gobert S, Porteu F, Pallu S, Muller O, Sabbah M, Dusanter-Fourt I, Courtois G, Lacombe C, Gisselbrecht S, Mayeux P. Tyrosine phosphorylation of the erythropoietin receptor: role for differentiation and mitogenic signal transduction. Blood. 1995;86:598–606. [PubMed] [Google Scholar]
- [15]Gronemeyer H. Transcription activation by estrogen and progesterone receptors. Annu Rev Genet. 1991;25:89–123. doi: 10.1146/annurev.ge.25.120191.000513. [DOI] [PubMed] [Google Scholar] · DOI
- [16]Gurney A L, Wong S C, Henzel W J, de Sauvage F J. Distinct regions of c-Mpl cytoplasmic domain are coupled to the JAK- STAT signal transduction pathway and Shc phosphorylation. Proc Natl Acad Sci USA. 1995;92:5292–5296. doi: 10.1073/pnas.92.12.5292. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- [18]Horvath C M, Stark G R, Kerr I M, Darnell J E., Jr Interactions between STAT and non-STAT proteins in the interferon-stimulated gene factor 3 transcription complex. Mol Cell Biol. 1996;16:6957–6964. doi: 10.1128/mcb.16.12.6957. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- [19]Hou J, Schindler U, Henzel W J, Ho T C, Brasseur M, McKnight S L. An interleukin-4-induced transcription factor: IL-4 Stat. Science. 1994;265:1701–1706. doi: 10.1126/science.8085155. [DOI] [PubMed] [Google Scholar] · DOI
- [20]Kaptein A, Paillard V, Saunders M. Dominant negative stat3 mutant inhibits interleukin-6-induced Jak-STAT signal transduction. J Biol Chem. 1996;271:5961–5964. doi: 10.1074/jbc.271.11.5961. [DOI] [PubMed] [Google Scholar] · DOI
- [21]Kishimoto T, Taga T, Akira S. Cytokine signal transduction. Cell. 1994;76:253–262. doi: 10.1016/0092-8674(94)90333-6. [DOI] [PubMed] [Google Scholar] · DOI
- [22]Kumar A, Commane M, Flickinger T W, Horvath C M, Stark G R. Defective TNF-alpha-induced apoptosis in STAT1-null cells due to low constitutive levels of caspases. Science. 1997;278:1630–1632. doi: 10.1126/science.278.5343.1630. [DOI] [PubMed] [Google Scholar] · DOI
- [23]Kumar V, Green S, Stack G, Berry M, Jin J R, Chambon P. Functional domains of the human estrogen receptor. Cell. 1987;51:941–951. doi: 10.1016/0092-8674(87)90581-2. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
- [24]Littlewood T D, Hancock D C, Danielian P S, Parker M G, Evan G I. A modified oestrogen receptor ligand-binding domain as an improved switch for the regulation of heterologous proteins. Nucleic Acids Res. 1995;23:1686–1690. doi: 10.1093/nar/23.10.1686. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- [25]Look D C, Pelletier M R, Holtzman M J. Selective interaction of a subset of interferon-gamma response element- binding proteins with the intercellular adhesion molecule-1 (ICAM-1) gene promoter controls the pattern of expression on epithelial cells. J Biol Chem. 1994;269:8952–8958. [PubMed] [Google Scholar]
- [26]Mattioni T, Louvion J F, Picard D. Regulation of protein activities by fusion to steroid binding domains. Methods Cell Biol. 1994;43:335–352. doi: 10.1016/s0091-679x(08)60611-1. [DOI] [PubMed] [Google Scholar] · DOI
- [27]McDonnell D P, Clemm D L, Hermann T, Goldman M E, Pike J W. Analysis of estrogen receptor function in vitro reveals three distinct classes of antiestrogens. Mol Endocrinol. 1995;9:659–669. doi: 10.1210/mend.9.6.8592512. [DOI] [PubMed] [Google Scholar] · DOI
- [28]McInerney E M, Katzenellenbogen B S. Different regions in activation function-1 of the human estrogen receptor required for antiestrogen- and estradiol-dependent transcription activation. J Biol Chem. 1996;271:24172–24178. doi: 10.1074/jbc.271.39.24172. [DOI] [PubMed] [Google Scholar] · DOI
- [29]McInerney E M, Weis K E, Sun J, Mosselman S, Katzenellenbogen B S. Transcription activation by the human estrogen receptor subtype beta (ER beta) studied with ER beta and ER alpha receptor chimeras. Endocrinology. 1998;139:4513–4522. doi: 10.1210/endo.139.11.6298. [DOI] [PubMed] [Google Scholar] · DOI
- [30]Metzger D, Ali S, Bornert J M, Chambon P. Characterization of the amino-terminal transcriptional activation function of the human estrogen receptor in animal and yeast cells. J Biol Chem. 1995;270:9535–9542. doi: 10.1074/jbc.270.16.9535. [DOI] [PubMed] [Google Scholar] · DOI
- [31]Metzger D, Losson R, Bornert J M, Lemoine Y, Chambon P. Promoter specificity of the two transcriptional activation functions of the human oestrogen receptor in yeast. Nucleic Acids Res. 1992;20:2813–2817. doi: 10.1093/nar/20.11.2813. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- [32]Minami M, Inoue M, Wei S, Takeda K, Matsumoto M, Kishimoto T, Akira S. STAT3 activation is a critical step in gp130-mediated terminal differentiation and growth arrest of a myeloid cell line. Proc Natl Acad Sci USA. 1996;93:3963–3966. doi: 10.1073/pnas.93.9.3963. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- [33]Miura Y, Miura O, Ihle J N, Aoki N. Activation of the mitogen-activated protein kinase pathway by the erythropoietin receptor. J Biol Chem. 1994;269:29962–29969. [PubMed] [Google Scholar]
- [34]Montano M M, Muller V, Trobaugh A, Katzenellenbogen B S. The carboxy-terminal F domain of the human estrogen receptor: role in the transcriptional activity of the receptor and the effectiveness of antiestrogens as estrogen antagonists. Mol Endocrinol. 1995;9:814–825. doi: 10.1210/mend.9.7.7476965. [DOI] [PubMed] [Google Scholar] · DOI
- [35]Moriggl R, Gouilleux-Gruart V, Jahne R, Berchtold S, Gartmann C, Liu X, Hennighausen L, Sotiropoulos A, Groner B, Gouilleux F. Deletion of the carboxyl-terminal transactivation domain of MGF-Stat5 results in sustained DNA binding and a dominant negative phenotype. Mol Cell Biol. 1996;16:5691–5700. doi: 10.1128/mcb.16.10.5691. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- [36]Morita H, Tahara T, Matsumoto A, Kato T, Miyazaki H, Ohashi H. Functional analysis of the cytoplasmic domain of the human Mpl receptor for tyrosine-phosphorylation of the signaling molecules, proliferation and differentiation. FEBS Lett. 1996;395:228–234. doi: 10.1016/0014-5793(96)01047-2. [DOI] [PubMed] [Google Scholar] · DOI
- [37]Muhlethaler-Mottet A, Di Berardino W, Otten L A, Mach B. Activation of the MHC class II transactivator CIITA by interferon-gamma requires cooperative interaction between Stat1 and USF-1. Immunity. 1998;8:157–166. doi: 10.1016/s1074-7613(00)80468-9. [DOI] [PubMed] [Google Scholar] · DOI
- [38]Muli A L, Wakao H, Kinoshita T, Kitamura T, Miyajima A. Suppression of interleukin-3-induced gene expression by a C-terminal truncated Stat5: role of Stat5 in proliferation. EMBO J. 1996;15:2425–2433. [PMC free article] [PubMed] [Google Scholar]
- [39]Muller M, Laxton C, Briscoe J, Schindler C, Improta T, Darnell J E, Jr, Stark G R, Kerr I M. Complementation of a mutant cell line: central role of the 91 kDa polypeptide of ISGF3 in the interferon-alpha and -gamma signal transduction pathways. EMBO J. 1993;12:4221–4228. doi: 10.1002/j.1460-2075.1993.tb06106.x. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI · Paper page
- [40]Nakajima K, Yamanaka Y, Nakae K, Kojima H, Ichiba M, Kiuchi N, Kitaoka T, Fukada T, Hibi M, Hirano T. A central role for Stat3 in IL-6-induced regulation of growth and differentiation in M1 leukemia cells. EMBO J. 1996;15:3651–3658. [PMC free article] [PubMed] [Google Scholar]
- [41]O’Farrell A M, Liu Y, Moore K W, Mui A L. IL-10 inhibits macrophage activation and proliferation by distinct signaling mechanisms: evidence for Stat3-dependent and -independent pathways. EMBO J. 1998;17:1006–1018. doi: 10.1093/emboj/17.4.1006. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- [42]Pernis A, Witthuhn B, Keegan A D, Nelms K, Garfein E, Ihle J N, Paul W E, Pierce J H, Rothman P. Interleukin 4 signals through two related pathways. Proc Natl Acad Sci USA. 1995;92:7971–7975. doi: 10.1073/pnas.92.17.7971. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- [43]Picard D, Kumar V, Chambon P, Yamamoto K R. Signal transduction by steroid hormones: nuclear localization is differentially regulated in estrogen and glucocorticoid receptors. Cell Regul. 1990;1:291–299. doi: 10.1091/mbc.1.3.291. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- [44]Picard D, Salser S J, Yamamoto K R. A movable and regulable inactivation function within the steroid binding domain of the glucocorticoid receptor. Cell. 1988;54:1073–1080. doi: 10.1016/0092-8674(88)90122-5. [DOI] [PubMed] [Google Scholar] · DOI
- [45]Pine R, Canova A, Schindler C. Tyrosine phosphorylated p91 binds to a single element in the ISGF2/IRF- 1 promoter to mediate induction by IFN alpha and IFN gamma, and is likely to autoregulate the p91 gene. EMBO J. 1994;13:158–167. doi: 10.1002/j.1460-2075.1994.tb06245.x. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI · Paper page
- [46]Piskurich J F, Wang Y, Linhoff M W, White L C, Ting J P. Identification of distinct regions of 5′ flanking DNA that mediate constitutive, IFN-gamma, STAT1, and TGF-beta-regulated expression of the class II transactivator gene. J Immunol. 1998;160:233–240. [PubMed] [Google Scholar]
- [47]Porteu F, Rouyez M C, Cocault L, Benit L, Charon M, Picard F, Gisselbrecht S, Souyri M, Dusanter-Fourt I. Functional regions of the mouse thrombopoietin receptor cytoplasmic domain: evidence for a critical region which is involved in differentiation and can be complemented by erythropoietin. Mol Cell Biol. 1996;16:2473–2482. doi: 10.1128/mcb.16.5.2473. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- [48]Quelle F W, Shimoda K, Thierfelder W, Fischer C, Kim A, Ruben S M, Cleveland J L, Pierce J H, Keegan A D, Nelms K, Paul W E, Ihle J N. Cloning of murine Stat6 and human Stat6, Stat proteins that are tyrosine phosphorylated in responses to IL-4 and IL-3 but are not required for mitogenesis. Mol Cell Biol. 1995;15:3336–3343. doi: 10.1128/mcb.15.6.3336. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- [49]Quelle F W, Wang D, Nosaka T, Thierfelder W E, Stravopodis D, Weinstein Y, Ihle J N. Erythropoietin induces activation of Stat5 through association with specific tyrosines on the receptor that are not required for a mitogenic response. Mol Cell Biol. 1996;16:1622–1631. doi: 10.1128/mcb.16.4.1622. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- [50]Raz R, Durbin J E, Levy D E. Acute phase response factor and additional members of the interferon-stimulated gene factor 3 family integrate diverse signals from cytokines, interferons, and growth factors. J Biol Chem. 1994;269:24391–24395. [PubMed] [Google Scholar]
- [51]Seidel H M, Milocco L H, Lamb P, Darnell J E, Jr, Stein R B, Rosen J. Spacing of palindromic half sites as a determinant of selective STAT (signal transducers and activators of transcription) DNA binding and transcriptional activity. Proc Natl Acad Sci USA. 1995;92:3041–3045. doi: 10.1073/pnas.92.7.3041. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI · Paper page
- [52]Seldin D C, Leder P. Mutational analysis of a critical signaling domain of the human interleukin 4 receptor. Proc Natl Acad Sci USA. 1994;91:2140–2144. doi: 10.1073/pnas.91.6.2140. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- [53]Shuai K, Halpern J, ten Hoeve J, Rao X, Sawyers C L. Constitutive activation of STAT5 by the BCR-ABL oncogene in chronic myelogenous leukemia. Oncogene. 1996;13:247–254. [PubMed] [Google Scholar]
- [54]Shuai K, Horvath C M, Huang L H, Qureshi S A, Cowburn D, Darnell J E., Jr Interferon activation of the transcription factor Stat91 involves dimerization through SH2-phosphotyrosyl peptide interactions. Cell. 1994;76:821–828. doi: 10.1016/0092-8674(94)90357-3. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
- [55]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;13:690–702. doi: 10.1128/mcb.13.1.690-702.1993. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- [56]Stark G R, Kerr I M, Williams B R, Silverman R H, Schreiber R D. How cells respond to interferons. Annu Rev Biochem. 1998;67:227–264. doi: 10.1146/annurev.biochem.67.1.227. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
- [57]Takatoku M, Kametaka M, Shimizu R, Miura Y, Komatsu N. Identification of functional domains of the human thrombopoietin receptor required for growth and differentiation of megakaryocytic cells. J Biol Chem. 1997;272:7259–7263. doi: 10.1074/jbc.272.11.7259. [DOI] [PubMed] [Google Scholar] · DOI
- [58]Taniguchi T, Lamphier M S, Tanaka N. IRF-1: the transcription factor linking the interferon response and oncogenesis. Biochim Biophys Acta. 1997;1333:M9–M17. doi: 10.1016/s0304-419x(97)00014-0. [DOI] [PubMed] [Google Scholar] · DOI
- [59]Teglund S, McKay C, Schuetz E, van Deursen J M, Stravopodis D, Wang D, Brown M, Bodner S, Grosveld G, Ihle J N. Stat5a and Stat5b proteins have essential and nonessential, or redundant, roles in cytokine responses. Cell. 1998;93:841–850. doi: 10.1016/s0092-8674(00)81444-0. [DOI] [PubMed] [Google Scholar] · DOI
- [60]Tian S S, Lamb P, Seidel H M, Stein R B, Rosen J. Rapid activation of the STAT3 transcription factor by granulocyte colony-stimulating factor. Blood. 1994;84:1760–1764. [PubMed] [Google Scholar]
- [61]Tian S S, Tapley P, Sincich C, Stein R B, Rosen J, Lamb P. Multiple signaling pathways induced by granulocyte colony-stimulating factor involving activation of JAKs, STAT5, and/or STAT3 are required for regulation of three distinct classes of immediate early genes. Blood. 1996;88:4435–4444. [PubMed] [Google Scholar]
- [62]Turkson J, Bowman T, Garcia R, Caldenhoven E, De Groot R P, Jove R. Stat3 activation by Src induces specific gene regulation and is required for cell transformation. Mol Cell Biol. 1998;18:2545–2552. doi: 10.1128/mcb.18.5.2545. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI · Paper page
- [63]Tzukerman M T, Esty A, Santiso-Mere D, Danielian P, Parker M G, Stein R B, Pike J W, McDonnell D P. Human estrogen receptor transactivational capacity is determined by both cellular and promoter context and mediated by two functionally distinct intramolecular regions. Mol Endocrinol. 1994;8:21–30. doi: 10.1210/mend.8.1.8152428. [DOI] [PubMed] [Google Scholar] · DOI
- [64]Vinkemeier U, Cohen S L, Moarefi I, Chait B T, Kuriyan J, Darnell J E., Jr DNA binding in vitro activated Stat1 alpha, Stat1 beta and truncated Stat1: interaction between NH2-terminal domains stabilizes binding of two dimers to tandem DNA sites. EMBO J. 1996;15:5616–5626. [PMC free article] [PubMed] [Google Scholar]
- [65]Wang D, Stravopodis D, Teglund S, Kitazawa J, Ihle J N. Naturally occurring dominant negative variants of Stat5. Mol Cell Biol. 1996;16:6141–6148. doi: 10.1128/mcb.16.11.6141. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- [66]Wang H, Peters G A, Zeng X, Tang M, Ip W, Khan S A. Yeast two-hybrid system demonstrates that estrogen receptor dimerization is ligand-dependent in vivo. J Biol Chem. 1995;270:23322–23329. doi: 10.1074/jbc.270.40.23322. [DOI] [PubMed] [Google Scholar] · DOI
- [67]Wang Y D, Wong K, Wood W I. Intracellular tyrosine residues of the human growth hormone receptor are not required for the signaling of proliferation or Jak-STAT activation. J Biol Chem. 1995;270:7021–7024. doi: 10.1074/jbc.270.13.7021. [DOI] [PubMed] [Google Scholar] · DOI
- [68]Webster N J, Green S, Jin J R, Chambon P. The hormone-binding domains of the estrogen and glucocorticoid receptors contain an inducible transcription activation function. Cell. 1988;54:199–207. doi: 10.1016/0092-8674(88)90552-1. [DOI] [PubMed] [Google Scholar] · DOI
- [69]Wen Z, Zhong Z, Darnell J E., Jr Maximal activation of transcription by Stat1 and Stat3 requires both tyrosine and serine phosphorylation. Cell. 1995;82:241–250. doi: 10.1016/0092-8674(95)90311-9. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
- [70]Xu X, Sun Y L, Hoey T. Cooperative DNA binding and sequence-selective recognition conferred by the STAT amino-terminal domain. Science. 1996;273:794–797. doi: 10.1126/science.273.5276.794. [DOI] [PubMed] [Google Scholar] · DOI
- [71]Ylikomi T, Bocquel M T, Berry M, Gronemeyer H, Chambon P. Cooperation of proto-signals for nuclear accumulation of estrogen and progesterone receptors. EMBO J. 1992;11:3681–3694. doi: 10.1002/j.1460-2075.1992.tb05453.x. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- [72]Zhang J J, Vinkemeier U, Gu W, Chakravarti D, Horvath C M, Darnell J E., Jr Two contact regions between Stat1 and CBP/p300 in interferon gamma signaling. Proc Natl Acad Sci USA. 1996;93:15092–15096. doi: 10.1073/pnas.93.26.15092. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- [73]Zhang Q, Nowak I, Vonderheid E C, Rook A H, Kadin M E, Nowell P C, Shaw L M, Wasik M A. Activation of Jak/STAT proteins involved in signal transduction pathway mediated by receptor for interleukin 2 in malignant T lymphocytes derived from cutaneous anaplastic large T-cell lymphoma and Sezary syndrome. Proc Natl Acad Sci USA. 1996;93:9148–9153. doi: 10.1073/pnas.93.17.9148. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
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Background
- Authors
- Milocco, L. H., Haslam, J. A., Rosen, J., & Seidel, H. M.
- Affiliations
- Ligand Pharmaceuticals (United States) (US)
- ORCID
- Rosen, Jonathan
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 1999-04-01
- Volume
- 19
- Issue
- 4
- Pages
- 2913-2920
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC84085
- OpenAlex
- W2120474497
- Cited by
- 52
- References
- 0
- Citations by year
- 2025: 1 · 2023: 1 · 2022: 1 · 2019: 1 · 2017: 1 · 2016: 1 · 2013: 2
- FWCI
- 3.03
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Molecular and Cellular Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- STAT signaling, tyrosine phosphorylation, nuclear localization signal, nuclear translocation, sequence-specific DNA binding, transcriptional activation, gene expression regulation, cytokine signaling
- MeSH terms
- Binding Sites, DNA-Binding Proteins, Estrogens, Interferon-gamma, Models, Molecular, Phosphoproteins, Phosphorylation, Protein Binding, Receptors, Estrogen, Recombinant Fusion Proteins, Tyrosine, Transcriptional Activation, Trans-Activators, Dimerization, STAT1 Transcription Factor, Interferon Regulatory Factor-1
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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