|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 278, Issue 19, 17218-17227, May 9, 2003
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Department of Molecular and Cellular Biology, Baylor
College of Medicine, Houston, Texas 77030-3498
Stat5 is activated by a broad spectrum of
cytokines, as well as non-receptor tyrosine kinases, such as Src. In
this study, the DNA binding properties of the two closely related Stat5
proteins, Stat5a and Stat5b, induced either by prolactin (Prl) or by
Src were analyzed by electrophoretic mobility shift assays using
several different Stat5 binding sites. Src-induced Stat5b-DNA binding complexes consistently displayed a slightly faster mobility than those
induced by Prl, as well as differences in their ability to be
supershifted by anti-Stat5 antibodies. IP-Westerns performed using
specific antibodies directed at the N and C termini of Stat5b suggested
that depending on the activating stimulus, Stat5b exhibited different
conformations, which influenced antibody accessibility at its C
terminus. These conformational differences may in part be due to
differential effects of Prl and Src on Stat5b tyrosine phosphorylation,
since Src induced several additional sites of tyrosine phosphorylation
of Stat5b at residues other than Tyr-699, including Tyr-724 and
Tyr-679. The latter Tyr-679 is conserved in all mammalian Stat5bs, but
is not present in Stat5a. A Stat 5bY679F mutant induced by Src kinase
exhibited an altered pattern of nuclear localization as compared with
wild-type Stat5b. Furthermore, this mutation inhibited v-Src-induced
cyclin D1-luciferase reporter activity in transient transfection assays
performed in Stat5a/b-deficient MEFs, suggesting that Tyr-679
phosphorylation may play a role in v-Src induced proliferation.
Thus, depending on the signal transduction pathway responsible
for activation, different conformations of activated Stat5 may result
in selective biological responses.
Signal Transduction Pathways Regulated by Prolactin and Src
Result in Different Conformations of Activated Stat5b*
*
This work was supported by Grant CA16303 from the NCI,
National Institutes of Health.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. Tel.: 713-798-6210;
Fax: 713-798-8012; E-mail: jrosen@bcm.tmc.edu.
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:
|
|
 |
|
  A. M. Weaver and C. M. Silva Modulation of Signal Transducer and Activator of Transcription 5b Activity in Breast Cancer Cells by Mutation of Tyrosines within the Transactivation Domain Mol. Endocrinol., October 1, 2006; 20(10): 2392 - 2405. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. B. Kabotyanski, M. Huetter, W. Xian, M. Rijnkels, and J. M. Rosen Integration of Prolactin and Glucocorticoid Signaling at the {beta}-Casein Promoter and Enhancer by Ordered Recruitment of Specific Transcription Factors and Chromatin Modifiers Mol. Endocrinol., October 1, 2006; 20(10): 2355 - 2368. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Ye, N. Wolff, L. Li, S. Zhang, and R. L. Ilaria Jr STAT5 signaling is required for the efficient induction and maintenance of CML in mice Blood, June 15, 2006; 107(12): 4917 - 4925. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Fang, E. M. Kofoed, B. M. Little, X. Wang, R. J. M. Ross, S. J. Frank, V. Hwa, and R. G. Rosenfeld A Mutant Signal Transducer and Activator of Transcription 5b, Associated with Growth Hormone Insensitivity and Insulin-Like Growth Factor-I Deficiency, Cannot Function as a Signal Transducer or Transcription Factor J. Clin. Endocrinol. Metab., April 1, 2006; 91(4): 1526 - 1534. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Y. Ma, G. M. Anderson, T. D. Gunn, V. Goffin, D. R. Grattan, and S. J. Bunn Prolactin Specifically Activates Signal Transducer and Activator of Transcription 5b in Neuroendocrine Dopaminergic Neurons Endocrinology, December 1, 2005; 146(12): 5112 - 5119. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Zhang, H. Y. Wang, M. Marzec, P. N. Raghunath, T. Nagasawa, and M. A. Wasik STAT3- and DNA methyltransferase 1-mediated epigenetic silencing of SHP-1 tyrosine phosphatase tumor suppressor gene in malignant T lymphocytes PNAS, May 10, 2005; 102(19): 6948 - 6953. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Hermoso, T. Matsuguchi, K. Smoak, and J. A. Cidlowski Glucocorticoids and Tumor Necrosis Factor Alpha Cooperatively Regulate Toll-Like Receptor 2 Gene Expression Mol. Cell. Biol., June 1, 2004; 24(11): 4743 - 4756. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Frame Newest findings on the oldest oncogene; how activated src does it J. Cell Sci., March 1, 2004; 117(7): 989 - 998. [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 |