| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Papers In Press, published online ahead of print February 13, 2004
Medicine/Infectious Diseases, Baylor College of Medicine, Houston, TX 77030
Corresponding Author: dtweardy{at}bcm.tmc.edu
Stat3 is an SH2-containing protein constitutively activated in a wide variety of human cancers following its recruitment to YXXQ-containing motifs, which results in resistance to apoptosis. Despite resolution of the crystal structure of Stat3 homodimer bound to DNA, the structural basis for the unique specificity of Stat3 SH2 for YXXQ-containing phosphopeptides remains unresolved. We tested three models of this interaction based on computational analysis of available structures and sequence alignments—two of which assumed an extended peptide configuration and one in which the peptide had a
J. Biol. Chem, 10.1074/jbc.M314037200
Submitted on December 22, 2003
Revised on February 2, 2004
Accepted on February 13, 2004
Structural requirements for signal transducer and activator of transcription 3 binding to phosphotyrosine ligands containing the YXXQ motif
turn. Using peptide immunoblot affinity assays and mirror resonance affinity analysis, we demonstrated that only phosphotyrosine (pY) peptides containing +3 Q (not L, M. E or R) bound to wild type Stat3. Examination of a series of wild type and mutant Stat3 proteins demonstrated loss of binding to pYXXQ-containing peptides only in Stat3 mutated at K589 or R607, whose side chains interact with the pY residue, and Stat3 mutated at E638, whose amide hydrogen bonds with oxygen within the +3 Q side chain when the peptide ligand assumes a turn. These findings support a model for Stat3 SH2 interactions that could form the basis for anticancer drugs that specifically target Stat3.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  G. R. Romeo and A. Kazlauskas Oxysterol and Diabetes Activate STAT3 and Control Endothelial Expression of Profilin-1 via OSBP1 J. Biol. Chem., April 11, 2008; 283(15): 9595 - 9605. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-S. Bong, H.-S. Lee, L. Carim-Todd, K. Mood, T. G. Nishanian, L. Tessarollo, and I. O. Daar ephrinB1 signals from the cell surface to the nucleus by recruitment of STAT3 PNAS, October 30, 2007; 104(44): 17305 - 17310. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Siddiquee, S. Zhang, W. C. Guida, M. A. Blaskovich, B. Greedy, H. R. Lawrence, M. L. R. Yip, R. Jove, M. M. McLaughlin, N. J. Lawrence, et al. Selective chemical probe inhibitor of Stat3, identified through structure-based virtual screening, induces antitumor activity PNAS, May 1, 2007; 104(18): 7391 - 7396. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 E. Heck, D. Lengenfelder, M. Schmidt, I. Muller-Fleckenstein, B. Fleckenstein, B. Biesinger, and A. Ensser T-Cell Growth Transformation by Herpesvirus Saimiri Is Independent of STAT3 Activation J. Virol., May 1, 2005; 79(9): 5713 - 5720. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
