|
Originally published In Press as doi:10.1074/jbc.M201842200 on March 1, 2002
J. Biol. Chem., Vol. 277, Issue 19, 17359-17366, May 10, 2002
Regulation of Erythropoietin-induced STAT Serine Phosphorylation
by Distinct Mitogen-activated Protein Kinases*
Rizwan
Haq §¶,
Adrienne
Halupa§ ,
Bryan K.
Beattie§,
Jacqueline M.
Mason§ ,
Brent W.
Zanke § ** , and
Dwayne L.
Barber§ §§¶¶
From the Institute of Medical Science,
Department of Medical Biophysics and
§§ Laboratory Medicine and Pathobiology,
University of Toronto, and § Ontario Cancer Institute,
Toronto, Ontario M5G 2M9, Canada and ** The Cross Cancer
Institute, Edmonton, Alberta T6G 1Z2, Canada
The STAT proteins are a family of latent
transcription factors that are activated by a wide variety of
cytokines. Upon receptor engagement, STATs become tyrosine
phosphorylated, translocate to the nucleus, and induce expression of
target genes. In addition to tyrosine phosphorylation, maximal
activation of some STAT proteins requires serine phosphorylation within
the transactivation domain. Here we focus on STAT phosphorylation after
engagement of the erythropoietin receptor (EPO-R). In Ba/F3-EPO-R
cells, EPO induces tyrosine and serine phosphorylation of STAT1, STAT3,
STAT5A, and STAT5B. Identical regions of the EPO-R couple to both
tyrosine and serine phosphorylation of each cognate STAT protein. A
proximal region of the EPO-R lacking cytoplasmic tyrosines couples to
STAT1 and STAT3 phosphorylation as well as ERK and p38HOG
activation, but not JNK/SAPK. STAT1 serine phosphorylation was perturbed by inhibition of ERK and p38 pathways, whereas only inhibition of ERK activation blocked STAT3 serine phosphorylation in
response to EPO. STAT5A/B phosphorylation is downstream of EPO-R
Tyr343, however, STAT5A/B serine phosphorylation is
unaffected by either ERK or p38 inhibition. Physiological responses
induced by EPO may depend on regulation of serine phosphorylation of
the STAT molecules by p38HOG and the ERK family of kinases
as well as additional serine/threonine kinases.
*
This work was supported in part by Leukemia Research Fund
(to B. W. Z.) and Canadian Institutes of Health Research
Grants 13612 (to D. L. B.) and MOP-36482 (to B. W. Z.).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.
¶
Supported by a Canadian Institutes of Health Research (CIHR)
MD/Ph.D. studentship.

To whom correspondence may be addressed.
¶¶
National Cancer Institute of Canada Research Scientist.
To whom correspondence may be addressed: Ontario Cancer Institute, 610 University Ave., Toronto, Ontario M5G 2M9, Canada. Tel.: 416-946-4455; Fax: 416-946-2065; E-mail: dbarber@uhnres.utoronto.ca.
Copyright © 2002 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:

|
 |

|
 |
 
N. C. Schmitt, E. W Rubel, and N. M. Nathanson
Cisplatin-Induced Hair Cell Death Requires STAT1 and Is Attenuated by Epigallocatechin Gallate
J. Neurosci.,
March 25, 2009;
29(12):
3843 - 3851.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Ni, C. Zhao, G.-S. Feng, R. F. Paulson, and P. H. Correll
A Novel Stat3 Binding Motif in Gab2 Mediates Transformation of Primary Hematopoietic Cells by the Stk/Ron Receptor Tyrosine Kinase in Response to Friend Virus Infection
Mol. Cell. Biol.,
May 15, 2007;
27(10):
3708 - 3715.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. P. Menon, J. Fang, and D. M. Wojchowski
Core erythropoietin receptor signals for late erythroblast development
Blood,
April 1, 2006;
107(7):
2662 - 2672.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Um and H. F. Lodish
Antiapoptotic Effects of Erythropoietin in Differentiated Neuroblastoma SH-SY5Y Cells Require Activation of Both the STAT5 and AKT Signaling Pathways
J. Biol. Chem.,
March 3, 2006;
281(9):
5648 - 5656.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
W. Komyod, U.-M. Bauer, P. C. Heinrich, S. Haan, and I. Behrmann
Are STATS Arginine-methylated?
J. Biol. Chem.,
June 10, 2005;
280(23):
21700 - 21705.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Halupa, M. L. Bailey, K. Huang, N. N. Iscove, D. E. Levy, and D. L. Barber
A novel role for STAT1 in regulating murine erythropoiesis: deletion of STAT1 results in overall reduction of erythroid progenitors and alters their distribution
Blood,
January 15, 2005;
105(2):
552 - 561.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. S. Argetsinger, J.-L. K. Kouadio, H. Steen, A. Stensballe, O. N. Jensen, and C. Carter-Su
Autophosphorylation of JAK2 on Tyrosines 221 and 570 Regulates Its Activity
Mol. Cell. Biol.,
June 1, 2004;
24(11):
4955 - 4967.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. K. H. Lo and Y. H. Wong
Signal Transducer and Activator of Transcription 3 Activation by the {delta}-Opioid Receptor via G{alpha}14 Involves Multiple Intermediates
Mol. Pharmacol.,
June 1, 2004;
65(6):
1427 - 1439.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C.-S. Shi and J. H. Kehrl
Pyk2 Amplifies Epidermal Growth Factor and c-Src-induced Stat3 Activation
J. Biol. Chem.,
April 23, 2004;
279(17):
17224 - 17231.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. J. Gu, K. Gathy, L. Santiago, E. Chen, M. Huang, L. M. Graves, and B. S. Mitchell
Induction of apoptosis in IL-3-dependent hematopoietic cell lines by guanine nucleotide depletion
Blood,
June 15, 2003;
101(12):
4958 - 4965.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
V. S. Cull, P. A. Tilbrook, E. J. Bartlett, N. L. Brekalo, and C. M. James
Type I interferon differential therapy for erythroleukemia: specificity of STAT activation
Blood,
April 1, 2003;
101(7):
2727 - 2735.
[Abstract]
[Full Text]
[PDF]
|
 |
|
Copyright © 2002 by the American Society for Biochemistry and Molecular Biology.
|
Advertisement
Advertisement
|