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Science 16 September 1994:
Vol. 265. no. 5179, pp. 1701 - 1706
DOI: 10.1126/science.8085155
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Articles

Science, Vol 265, Issue 5179, 1701-1706
Copyright © 1994 by American Association for the Advancement of Science

articles

An interleukin-4-induced transcription factor: IL-4 Stat

J Hou, U Schindler, WJ Henzel, TC Ho, M Brasseur, and SL McKnight

Tularik, Inc., South San Francisco, CA 94080.

Interleukin-4 (IL-4) is an immunomodulatory cytokine secreted by activated T lymphocytes, basophils, and mast cells. It plays an important role in modulating the balance of T helper (Th) cell subsets, favoring expansion of the Th2 lineage relative to Th1. Imbalance of these T lymphocyte subsets has been implicated in immunological diseases including allergy, inflammation, and autoimmune disease. IL-4 may mediate its biological effects, at least in part, by activating a tyrosine-phosphorylated DNA binding protein. This protein has now been purified and its encoding gene cloned. Examination of the primary amino acid sequence of this protein indicates that it is a member of the signal transducers and activators of transcription (Stat) family of DNA binding proteins, hereby designated IL-4 Stat. Study of the inhibitory activities of phosphotyrosine-containing peptides derived from the intracellular domain of the IL-4 receptor provided evidence for direct coupling of receptor and transcription factor during the IL-4 Stat activation cycle. Such observations indicate that IL-4 Stat has the same functional domain for both receptor coupling and dimerization.


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J. Immunol. 163, 4192-4198
   Abstract »    Full Text »    PDF »
Functional Synergism of STAT6 with Either NF-{kappa}B or PU.1 to Mediate IL-4-Induced Activation of IgE Germline Gene Transcription.
A. M. Stutz and M. Woisetschlager (1999)
J. Immunol. 163, 4383-4391
   Abstract »    Full Text »    PDF »
Induction of 3{beta}-Hydroxysteroid Dehydrogenase/ Isomerase Type 1 Expression by Interleukin-4 in Human Normal Prostate Epithelial Cells, Immortalized Keratinocytes, Colon, and Cervix Cancer Cell Lines.
S. Gingras and J. Simard (1999)
Endocrinology 140, 4573-4584
   Abstract »    Full Text »
IFN-{alpha} Activates Stat6 and Leads to the Formation of Stat2:Stat6 Complexes in B Cells.
S. Gupta, M. Jiang, and A. B. Pernis (1999)
J. Immunol. 163, 3834-3841
   Abstract »    Full Text »    PDF »
Interferons inhibit activation of STAT6 by interleukin 4 in human monocytes by inducing SOCS-1 gene expression.
H. L. Dickensheets, C. Venkataraman, U. Schindler, and R. P. Donnelly (1999)
PNAS 96, 10800-10805
   Abstract »    Full Text »    PDF »
BCL-6-Deficient Mice Reveal an IL-4-Independent, STAT6-Dependent Pathway That Controls Susceptibility to Infection by Leishmania major.
A. L. Dent, T. M. Doherty, W. E. Paul, A. Sher, and L. M. Staudt (1999)
J. Immunol. 163, 2098-2103
   Abstract »    Full Text »    PDF »
STAT6-Deficient Mice Exhibit Normal Induction of Murine AIDS and Expression of Immunoglobulin E following Infection with LP-BM5 Murine Leukemia Viruses.
H. C. Morse III, T. McCarty, N. A. Giese, L. Taddesse-Heath, and M. J. Grusby (1999)
J. Virol. 73, 7093-7095
   Abstract »    Full Text »
Altered Memory T Cell Differentiation in Patients with Early Rheumatoid Arthritis.
A. Skapenko, J. Wendler, P. E. Lipsky, J. R. Kalden, and H. Schulze-Koops (1999)
J. Immunol. 163, 491-499
   Abstract »    Full Text »    PDF »
Design of Conditionally Active STATs: Insights into STAT Activation and Gene Regulatory Function.
L. H. Milocco, J. A. Haslam, J. Rosen, and H. M. Seidel (1999)
Mol. Cell. Biol. 19, 2913-2920
   Abstract »    Full Text »    PDF »
Repression of IL-4-Induced Gene Expression by IFN-{gamma} Requires Stat1 Activation.
C. Venkataraman, S. Leung, A. Salvekar, H. Mano, and U. Schindler (1999)
J. Immunol. 162, 4053-4061
   Abstract »    Full Text »    PDF »
Interleukin-12 Induces Expression of Interferon Regulatory Factor-1 via Signal Transducer and Activator of Transcription-4 in Human T Helper Type 1 Cells.
E. M. Coccia, N. Passini, A. Battistini, C. Pini, F. Sinigaglia, and L. Rogge (1999)
J. Biol. Chem. 274, 6698-6703
   Abstract »    Full Text »    PDF »
IL-4 Preferentially Activates a Novel STAT6 Isoform in Mast Cells.
M. A. Sherman, V. H. Secor, and M. A. Brown (1999)
J. Immunol. 162, 2703-2708
   Abstract »    Full Text »    PDF »
IL-2, But Not IL-4 and Other Cytokines, Induces Phosphorylation of a 98-kDa Protein Associated with SHP-2, Phosphatidylinositol 3'-Kinase, and Grb2.
M. Gadina, C. Sudarshan, and J. J. O'Shea (1999)
J. Immunol. 162, 2081-2086
   Abstract »    Full Text »    PDF »
Identification of a STAT4 Binding Site in the Interleukin-12 Receptor Required for Signaling.
L. K. Naeger, J. McKinney, A. Salvekar, and T. Hoey (1999)
J. Biol. Chem. 274, 1875-1878
   Abstract »    Full Text »    PDF »
Induction of 3{beta}-Hydroxysteroid Dehydrogenase/{Delta}5-{Delta}4 Isomerase Type 1 Gene Transcription in Human Breast Cancer Cell Lines and in Normal Mammary Epithelial Cells by Interleukin-4 and Interleukin-13.
S. Gingras, R. Moriggl, B. Groner, and J. Simard (1999)
Mol. Endocrinol. 13, 66-81
   Abstract »    Full Text »
The PTK-STAT Signaling Pathway Has Essential Roles in T-cell Activation in Response to Antigen Stimulation.
T. WELTE, D. LEITENBERG, B.N. DITTEL, B.K. AL-RAMADI, W.R. HANSEN, B. XIE, C.A. JANEWAY, A.L.M. BOTHWELL, K. BOTTOMLY, and X.Y. FU (1999)
Cold Spring Harb Symp Quant Biol 64, 291-302
   Abstract »    PDF »
Presence or Absence of TGF-{beta} Determines IL-4-Induced Generation of Type 1 or Type 2 CD8 T Cell Subsets.
F. Erard, J. A. Garcia-Sanz, R. Moriggl, and M.-T. Wild (1999)
J. Immunol. 162, 209-214
   Abstract »    Full Text »    PDF »
Identification of a Novel Stat3 Recruitment and Activation Motif Within the Granulocyte Colony-Stimulating Factor Receptor.
A. Chakraborty, K. F. Dyer, M. Cascio, T. A. Mietzner, and D. J. Tweardy (1999)
Blood 93, 15-24
   Abstract »    Full Text »    PDF »
Tyrosine-Dependent and -Independent Mechanisms of STAT3 Activation by the Human Granulocyte Colony-Stimulating Factor (G-CSF) Receptor Are Differentially Utilized Depending on G-CSF Concentration.
A. C. Ward, M. H.A. Hermans, L. Smith, Y. M. van Aesch, A. M. Schelen, C. Antonissen, and I. P. Touw (1999)
Blood 93, 113-124
   Abstract »    Full Text »    PDF »
Protein-tyrosine Phosphatase Shp-1 Is a Negative Regulator of IL-4- and IL-13-dependent Signal Transduction.
S. J. Haque, P. Harbor, M. Tabrizi, T. Yi, and B. R. G. Williams (1998)
J. Biol. Chem. 273, 33893-33896
   Abstract »    Full Text »    PDF »
The Role of Stat4 in Species-Specific Regulation of Th Cell Development by Type I IFNs.
L. Rogge, D. D'Ambrosio, M. Biffi, G. Penna, L. J. Minetti, D. H. Presky, L. Adorini, and F. Sinigaglia (1998)
J. Immunol. 161, 6567-6574
   Abstract »    Full Text »    PDF »


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