JBC

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1074/jbc.M300261200 on February 18, 2003

J. Biol. Chem., Vol. 278, Issue 18, 16117-16128, May 2, 2003
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
278/18/16117    most recent
M300261200v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wiederkehr-Adam, M.
Right arrow Articles by Heim, M. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wiederkehr-Adam, M.
Right arrow Articles by Heim, M. H.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Characterization of Phosphopeptide Motifs Specific for the Src Homology 2 Domains of Signal Transducer and Activator of Transcription 1 (STAT1) and STAT3*

Michèle Wiederkehr-AdamDagger §, Philipp ErnstDagger §, Kurt Müller, Elke BieckDagger , Frank O. Gombert, Johannes Ottl||, Patrick Graff, Fred Grossmüller**, and Markus H. HeimDagger Dagger Dagger

From the Dagger  Department of Research, University Hospital Basel, CH-4031 Basel,  Novartis Pharma AG, CH-4002 Basel, Switzerland, || Max Planck Institute of Biochemistry, D-82152 Martinsried, Germany, and ** Novartis Research Institute, A-1235 Vienna, Austria

Signal transducers and activators of transcription (STAT) 1 and STAT3 are activated by overlapping but distinct sets of cytokines. STATs are recruited to the different cytokine receptors through their Src homology (SH) 2 domains that make highly specific interactions with phosphotyrosine-docking sites on the receptors. We used a degenerate phosphopeptide library synthesized on 35-µm TentaGel beads and fluorescence-activated bead sorting to determine the sequence specificity of the peptide-binding sites of the SH2 domains of STAT1 and STAT3. The large bead library allowed not only peptide sequencing of pools of beads but also of single beads. The method was validated through surface plasmon resonance measurements of the affinities of different peptides to the STAT SH2 domains. Furthermore, when selected peptides were attached to a truncated erythropoietin receptor and stably expressed in DA3 cells, activation of STAT1 or STAT3 could be achieved by stimulation with erythropoietin. The combined analysis of pool sequencing, the individual peptide sequences, and plasmon resonance measurements allowed the definition of SH2 domain binding motifs. STAT1 preferentially binds peptides with the motif phosphotyrosine-(aspartic acid/glutamic acid)-(proline/arginine)-(arginine/proline/glutamine), whereby a negatively charged amino acid at +1 excludes a proline at +2 and vice versa. STAT3 preferentially binds peptides with the motif phosphotyrosine-(basic or hydrophobic)-(proline or basic)-glutamine. For both STAT1 and STAT3, specific high affinity phosphopeptides were identified that can be used for the design of inhibitory molecules.

* This work was supported by Swiss National Science Foundation Grants 3200-052626.97 and 32-54973.98, by the Sandoz-Stiftung zur Förderung der Medizinisch-Biologischen Wissenschaften, and by the Freiwillige Akademische Gesellschaft Basel.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.

§ Both authors contributed equally to this work.

Dagger Dagger To whom correspondence should be addressed: Zentrum für Lehre und Forschung, Kantonsspital Basel, Hebelstrasse 20, CH-4031 Basel, Switzerland. Tel.: 41-61-265-33-62; Fax: 41-61-265-23-50; E-mail: Markus.Heim@unibas.ch.

Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 Mol. Cell. ProteomicsHome page
H. Huang, L. Li, C. Wu, D. Schibli, K. Colwill, S. Ma, C. Li, P. Roy, K. Ho, Z. Songyang, et al.
Defining the Specificity Space of the Human Src Homology 2 Domain
Mol. Cell. Proteomics, April 1, 2008; 7(4): 768 - 784.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
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]

Home page
 J. Immunol.Home page
H. Shao, X. Xu, N. Jing, and D. J. Tweardy
Unique structural determinants for stat3 recruitment and activation by the granulocyte colony-stimulating factor receptor at phosphotyrosine ligands 704 and 744.
J. Immunol., March 1, 2006; 176(5): 2933 - 2941.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
N. Martens, G. Uzan, M. Wery, R. Hooghe, E. L. Hooghe-Peters, and A. Gertler
Suppressor of Cytokine Signaling 7 Inhibits Prolactin, Growth Hormone, and Leptin Signaling by Interacting with STAT5 or STAT3 and Attenuating Their Nuclear Translocation
J. Biol. Chem., April 8, 2005; 280(14): 13817 - 13823.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Y. Qing and G. R. Stark
Alternative Activation of STAT1 and STAT3 in Response to Interferon-{gamma}
J. Biol. Chem., October 1, 2004; 279(40): 41679 - 41685.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
N. Jing, Y. Li, W. Xiong, W. Sha, L. Jing, and D. J. Tweardy
G-Quartet Oligonucleotides: A New Class of Signal Transducer and Activator of Transcription 3 Inhibitors That Suppresses Growth of Prostate and Breast Tumors through Induction of Apoptosis
Cancer Res., September 15, 2004; 64(18): 6603 - 6609.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. Dreuw, S. Radtke, S. Pflanz, B. E. Lippok, P. C. Heinrich, and H. M. Hermanns
Characterization of the Signaling Capacities of the Novel gp130-like Cytokine Receptor
J. Biol. Chem., August 20, 2004; 279(34): 36112 - 36120.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
H. Shao, X. Xu, M.-A. A. Mastrangelo, N. Jing, R. G. Cook, G. B. Legge, and D. J. Tweardy
Structural Requirements for Signal Transducer and Activator of Transcription 3 Binding to Phosphotyrosine Ligands Containing the YXXQ Motif
J. Biol. Chem., April 30, 2004; 279(18): 18967 - 18973.
[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 
Copyright © 2003 by the American Society for Biochemistry and Molecular Biology.