|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 95 No. 2 (January 15), 2000:
pp. 494-502
Interleukin-4-induced transcriptional activation by Stat6 involves
multiple serine/threonine kinase pathways and serine phosphorylation of
Stat6
Marko Pesu,
Kati Takaluoma,
Saara Aittomäki,
Anssi Lagerstedt,
Kalle Saksela,
Panu E. Kovanen, and
Olli Silvennoinen
From the Laboratory of Molecular Immunology, Department of
Pathology, Laboratory of Molecular Medicine, Institute of Medical
Technology, University of Tampere, and the Department of Clinical
Microbiology, Tampere University Hospital, Finland.
Stat6 transcription factor is a critical mediator of IL-4-specific
gene responses. Tyrosine phosphorylation is required for nuclear
localization and DNA binding of Stat6. The authors investigated whether
Stat6-dependent transcriptional responses are regulated through
IL-4-induced serine/threonine phosphorylation. In Ramos B
cells, the serine/threonine kinase inhibitor H7 inhibited IL-4-induced expression of CD23. Treatment with H7 did not affect IL-4R-mediated immediate signaling events such as tyrosine phosphorylation of Jak1,
Jak3, insulin receptor substrate (IRS)-1 and IRS-2, or tyrosine phosphorylation and DNA binding of Stat6. To analyze whether the H7-sensitive pathway was regulating Stat6-activated transcription, we
used reporter constructs containing different IL-4 responsive elements.
H7 abrogated Stat6-, as well as Stat5-, mediated reporter gene
activation and partially reduced C/EBP-dependent reporter activity. By
contrast, IL-4-induced transcription was not affected by wortmannin, an
inhibitor of the phosphatidyl-inositol 3'-kinase pathway. Phospho-amino
acid analysis and tryptic phosphopeptide maps revealed that IL-4
induced phosphorylation of Stat6 on serine and tyrosine residues in
Ramos cells and in 32D cells lacking endogenous IRS proteins. However,
H7 treatment did not inhibit the phosphorylation of Stat6. Instead, H7
inhibited the IL-4-induced phosphorylation of RNA polymerase II. These
results indicate that Stat6-induced transcription is dependent on
phosphorylation events mediated by H7-sensitive kinase(s) but that it
also involves serine phosphorylation of Stat6 by an H7-insensitive
kinase independent of the IRS pathway.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
S. Bessoles, F. Fouret, S. Dudal, G. S. Besra, F. Sanchez, and V. Lafont
IL-2 triggers specific signaling pathways in human NKT cells leading to the production of pro- and anti-inflammatory cytokines
J. Leukoc. Biol.,
July 1, 2008;
84(1):
224 - 233.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. S. Rahman, A. Yamasaki, J. Yang, L. Shan, A. J. Halayko, and A. S. Gounni
IL-17A Induces Eotaxin-1/CC Chemokine Ligand 11 Expression in Human Airway Smooth Muscle Cells: Role of MAPK (Erk1/2, JNK, and p38) Pathways
J. Immunol.,
September 15, 2006;
177(6):
4064 - 4071.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Valineva, J. Yang, and O. Silvennoinen
Characterization of RNA helicase A as component of STAT6-dependent enhanceosome
Nucleic Acids Res.,
September 1, 2006;
34(14):
3938 - 3946.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Pesu, L. Muul, Y. Kanno, and J. J. O'Shea
Proprotein convertase furin is preferentially expressed in T helper 1 cells and regulates interferon gamma
Blood,
August 1, 2006;
108(3):
983 - 985.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Valineva, J. Yang, R. Palovuori, and O. Silvennoinen
The Transcriptional Co-activator Protein p100 Recruits Histone Acetyltransferase Activity to STAT6 and Mediates Interaction between the CREB-binding Protein and STAT6
J. Biol. Chem.,
April 15, 2005;
280(15):
14989 - 14996.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Kojima, T. Sasaki, T. Ishitani, S.-i. Iemura, H. Zhao, S. Kaneko, H. Kunimoto, T. Natsume, K. Matsumoto, and K. Nakajima
STAT3 regulates Nemo-like kinase by mediating its interaction with IL-6-stimulated TGF{beta}-activated kinase 1 for STAT3 Ser-727 phosphorylation
PNAS,
March 22, 2005;
102(12):
4524 - 4529.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Wang, M. G. Malabarba, Z. S. Nagy, and R. A. Kirken
Interleukin 4 Regulates Phosphorylation of Serine 756 in the Transactivation Domain of Stat6: ROLES FOR MULTIPLE PHOSPHORYLATION SITES AND Stat6 FUNCTION
J. Biol. Chem.,
June 11, 2004;
279(24):
25196 - 25203.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Takamura, Y. Nasuhara, M. Kobayashi, T. Betsuyaku, Y. Tanino, I. Kinoshita, E. Yamaguchi, S. Matsukura, R. P. Schleimer, and M. Nishimura
Retinoic acid inhibits interleukin-4-induced eotaxin production in a human bronchial epithelial cell line
Am J Physiol Lung Cell Mol Physiol,
April 1, 2004;
286(4):
L777 - L785.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Zamorano, M. D. Rivas, A. Garcia-Trinidad, C.-K. Qu, and A. D. Keegan
Phosphatidylcholine-Specific Phospholipase C Activity Is Necessary for the Activation of STAT6
J. Immunol.,
October 15, 2003;
171(8):
4203 - 4209.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Paukku, J. Yang, and O. Silvennoinen
Tudor and Nuclease-Like Domains Containing Protein p100 Function as Coactivators for Signal Transducer and Activator of Transcription 5
Mol. Endocrinol.,
September 1, 2003;
17(9):
1805 - 1814.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Woetmann, J. Brockdorff, P. Lovato, M. Nielsen, V. Leick, K. Rieneck, A. Svejgaard, C. Geisler, and N. Odum
Protein Phosphatase 2A (PP2A) Regulates Interleukin-4-mediated STAT6 Signaling
J. Biol. Chem.,
January 24, 2003;
278(5):
2787 - 2791.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H.-H. Xue, D. W. Fink Jr, X. Zhang, J. Qin, C. W. Turck, and W. J. Leonard
Serine phosphorylation of Stat5 proteins in lymphocytes stimulated with IL-2
Int. Immunol.,
November 1, 2002;
14(11):
1263 - 1271.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Pesu, S. Aittomaki, K. Takaluoma, A. Lagerstedt, and O. Silvennoinen
p38 Mitogen-activated Protein Kinase Regulates Interleukin-4-induced Gene Expression by Stimulating STAT6-mediated Transcription
J. Biol. Chem.,
October 4, 2002;
277(41):
38254 - 38261.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Crepaldi, L. Silveri, F. Calzetti, C. Pinardi, and M. A. Cassatella
Molecular basis of the synergistic production of IL-1 receptor antagonist by human neutrophils stimulated with IL-4 and IL-10
Int. Immunol.,
October 1, 2002;
14(10):
1145 - 1153.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Perez-G., M. Melo, A. D. Keegan, and J. Zamorano
Aspirin and Salicylates Inhibit the IL-4- and IL-13-Induced Activation of STAT6
J. Immunol.,
February 1, 2002;
168(3):
1428 - 1434.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Bhattacharya, B. A. Stout, M. E. Bates, P. J. Bertics, and J. S. Malter
Granulocyte Macrophage Colony-Stimulating Factor and Interleukin-5 Activate STAT5 and Induce CIS1 mRNA in Human Peripheral Blood Eosinophils
Am. J. Respir. Cell Mol. Biol.,
March 1, 2001;
24(3):
312 - 316.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Kotaja, S. Aittomäki, O. Silvennoinen, J. J. Palvimo, and O. A. Jänne
ARIP3 (Androgen Receptor-Interacting Protein 3) and Other PIAS (Protein Inhibitor of Activated STAT) Proteins Differ in Their Ability to Modulate Steroid Receptor-Dependent Transcriptional Activation
Mol. Endocrinol.,
December 1, 2000;
14(12):
1986 - 2000.
[Abstract]
[Full Text]
|
|
|
| |
