|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 278, Issue 6, 3903-3911, February 7, 2003
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the ** Department of Immunology and
Signal transducer and activator of transcription
6 (Stat6) plays an important role in interleukin (IL)-4-induced
responses. To analyze the regulation of Stat6 phosphorylation, cells
were cultured in the continuous presence of IL-4 or after a pulse and washout. In the continual presence of IL-4, Stat6 remained
phosphorylated for an extended period. After IL-4 removal and
inhibition of the Janus family kinase, tyrosine-phosphorylated Stat6
decayed at a rate dependent upon the length of IL-4 stimulation. The
decay of tyrosine-phosphorylated Stat6 was similar in the presence or absence of either cycloheximide or actinomycin D. In the absence of
functional Src homology-containing phosphatase-1 (SHP-1), the early
loss of tyrosine-phosphorylated Stat6 was substantially reduced.
Furthermore, the rate of loss of tyrosine-phosphorylated Stat6 in cells
expressing a mutation of the human IL-4 receptor
Regulation of the Dephosphorylation of Stat6
PARTICIPATION OF TYR-713 IN THE INTERLEUKIN-4 RECEPTOR 
, THE
TYROSINE PHOSPHATASE SHP-1, AND THE PROTEASOME*
§**,
,**
Department of Hematopoiesis, Holland Laboratory, American Red
Cross, Rockville, Maryland 20855, Institute of
Biomedical Sciences, George Washington University Medical Center,
and ¶ Center for Biologics Evaluation and Research, Federal Drug
Administration, Bethesda, Maryland 20892
in the
immunoreceptor tyrosine-based inhibitory motif sequence (Y5F) was
dramatically decreased compared with wild-type cells. The early rate of
decay was similar in the presence or absence of MG132, an inhibitor of
the proteasome, but the later rate of decay was decreased 5-fold. These
results suggest that the loss of tyrosine phosphorylation of Stat6 is
regulated by the action of SHP-1 and the proteasome but is not
dependent on new protein synthesis.
*
This work was supported by National Institutes of Health
Grant AI38985 (to A. D. K.), by The George Washington Institute of Biomedical Sciences (to E. M. H.), and by the American Red Cross.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Dept. of
Immunology, Holland Laboratory, American Red Cross, 15601 Crabbs Branch Way, Rockville, MD 20855. Tel.: 301-517-0326; Fax: 301-517-0344; E-mail: KeeganA@usa.redcross.org.
Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Y. Oh, T. Zheng, Y.-K. Kim, L. Cohn, R. J. Homer, A. N. J. McKenzie, and Z. Zhu A Critical Role of SHP-1 in Regulation of Type 2 Inflammation in the Lung Am. J. Respir. Cell Mol. Biol., May 1, 2009; 40(5): 568 - 574. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. P. Christophi, C. A. Hudson, M. Panos, R. C. Gruber, and P. T. Massa Modulation of Macrophage Infiltration and Inflammatory Activity by the Phosphatase SHP-1 in Virus-Induced Demyelinating Disease J. Virol., January 15, 2009; 83(2): 522 - 539. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Lu, R. Malumbres, B. Shields, X. Jiang, K. A. Sarosiek, Y. Natkunam, T. Tiganis, and I. S. Lossos PTP1B is a negative regulator of interleukin 4-induced STAT6 signaling Blood, November 15, 2008; 112(10): 4098 - 4108. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Lu, J. Chen, R. T. Sasmono, E. D. Hsi, K. A. Sarosiek, T. Tiganis, and I. S. Lossos T-Cell Protein Tyrosine Phosphatase, Distinctively Expressed in Activated-B-Cell-Like Diffuse Large B-Cell Lymphomas, Is the Nuclear Phosphatase of STAT6 Mol. Cell. Biol., March 15, 2007; 27(6): 2166 - 2179. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Han, H. M. Amin, B. Franko, C. Frantz, X. Shi, and R. Lai Loss of SHP1 enhances JAK3/STAT3 signaling and decreases proteosome degradation of JAK3 and NPM-ALK in ALK+ anaplastic large-cell lymphoma Blood, October 15, 2006; 108(8): 2796 - 2803. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Kozma, M. Halasz, B. Polgar, T. G. Poehlmann, U. R. Markert, T. Palkovics, M. Keszei, G. Par, K. Kiss, J. Szeberenyi, et al. Progesterone-Induced Blocking Factor Activates STAT6 via Binding to a Novel IL-4 Receptor J. Immunol., January 15, 2006; 176(2): 819 - 826. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. Stephenson, D.-S. Park, A. L. Mora, S. Goenka, and M. Boothby Sequence Motifs in IL-4R{alpha} Mediating Cell-Cycle Progression of Primary Lymphocytes J. Immunol., October 15, 2005; 175(8): 5178 - 5185. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Kelly-Welch, E. M. Hanson, and A. D. Keegan Interleukin-4 (IL-4) Pathway Sci. Signal., July 19, 2005; 2005(293): cm9 - cm9. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Lu, H. Nechushtan, F. Ding, M. F. Rosado, R. Singal, A. A. Alizadeh, and I. S. Lossos Distinct IL-4-induced gene expression, proliferation, and intracellular signaling in germinal center B-cell-like and activated B-cell-like diffuse large-cell lymphomas Blood, April 1, 2005; 105(7): 2924 - 2932. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Zamorano, M. D. Rivas, F. Setien, and M. Perez-G Proteolytic Regulation of Activated STAT6 by Calpains J. Immunol., March 1, 2005; 174(5): 2843 - 2848. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Huang, J. Xin, J. Coleman, and H. Huang IFN-{gamma} Suppresses STAT6 Phosphorylation by Inhibiting Its Recruitment to the IL-4 Receptor J. Immunol., February 1, 2005; 174(3): 1332 - 1337. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W.-M. Yu, S. Wang, A. D. Keegan, M. S. Williams, and C.-K. Qu Abnormal Th1 Cell Differentiation and IFN-{gamma} Production in T Lymphocytes from Motheaten Viable Mice Mutant for Src Homology 2 Domain-Containing Protein Tyrosine Phosphatase-1 J. Immunol., January 15, 2005; 174(2): 1013 - 1019. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Guiter, I. Dusanter-Fourt, C. Copie-Bergman, M.-L. Boulland, S. le Gouvello, P. Gaulard, K. Leroy, and F. Castellano Constitutive STAT6 activation in primary mediastinal large B-cell lymphoma Blood, July 15, 2004; 104(2): 543 - 549. [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]
|
|
|
|
|
|
W. Chen, M. O. Daines, and G. K. K. Hershey Methylation of STAT6 Modulates STAT6 Phosphorylation, Nuclear Translocation, and DNA-Binding Activity J. Immunol., June 1, 2004; 172(11): 6744 - 6750. [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]
|
|
|
|
 |
|
 A. E. Kelly-Welch, E. M. Hanson, M. R. Boothby, and A. D. Keegan Interleukin-4 and Interleukin-13 Signaling Connections Maps Science, June 6, 2003; 300(5625): 1527 - 1528. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |