JBC American Association for Cancer Research Centennial

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


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
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 Oligino, L.
Right arrow Articles by King, C. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Oligino, L.
Right arrow Articles by King, C. R.
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?

Volume 272, Number 46, Issue of November 14, 1997 pp. 29046-29052
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

Nonphosphorylated Peptide Ligands for the Grb2 Src Homology 2 Domain

(Received for publication, May 8, 1997, and in revised form, July 30, 1997)

Lyn Oligino Dagger , Feng-Di T. Lung , Lakshmi Sastry par , James Bigelow Dagger , Tin Cao par , Michael Curran Dagger , Terrence R. Burke Jr. , Shaomeng Wang ** , David Krag Dagger , Peter P. Roller and C. Richter King par

From the Dagger  Vermont Cancer Center, University of Vermont, Burlington, Vermont 05405;  Laboratory of Medicinal Chemistry, Division of Basic Sciences, NCI, National Institutes of Health, Bethesda, Maryland 20892; par  Lombardi Cancer Center, Georgetown University Medical Center, Washington, D. C. 20007; and the ** Department of Neurology, Georgetown University Medical Center, Washington, D. C. 20007

Critical intracellular signals in normal and malignant cells are transmitted by the adaptor protein Grb2 by means of its Src homology 2 (SH2) domain, which binds to phosphotyrosyl (pTyr) residues generated by the activation of tyrosine kinases. To understand this important control point and to design inhibitors, previous investigations have focused on the molecular mechanisms by which the Grb2 SH2 domain selectively binds pTyr containing peptides. In the current study, we demonstrate that the Grb2 SH2 domain can also bind in a pTyr independent manner. Using phage display, an 11-amino acid cyclic peptide, G1, has been identified that binds to the Grb2 SH2 domain but not the src SH2 domain. Synthetic G1 peptide blocks Grb2 SH2 domain association (IC50 10-25 µM) with a 9-amino acid pTyr-containing peptide derived from the SHC protein (pTyr317). These data and amino acid substitution analysis indicate that G1 interacts in the phosphopeptide binding site. G1 peptide requires a YXN sequence similar to that found in natural pTyr-containing ligands, and phosphorylation of the tyrosine increases G1 inhibitory activity. G1 also requires an internal disulfide bond to maintain the active binding conformation. Since the G1 peptide does not contain pTyr, it defines a new type of SH2 domain binding motif that may advance the design of Grb2 antagonists.


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
 Cancer Res.Home page
D. N. Krag, G. S. Shukla, G.-P. Shen, S. Pero, T. Ashikaga, S. Fuller, D. L. Weaver, S. Burdette-Radoux, and C. Thomas
Selection of Tumor-binding Ligands in Cancer Patients with Phage Display Libraries.
Cancer Res., August 1, 2006; 66(15): 7724 - 7733.
[Abstract] [Full Text] [PDF]

Home page
 JNCI J Natl Cancer InstHome page
S. Tanaka, S. C. Pero, K. Taguchi, M. Shimada, M. Mori, D. N. Krag, and S. Arii
Specific Peptide ligand for grb7 signal transduction protein and pancreatic cancer metastasis.
J Natl Cancer Inst, April 5, 2006; 98(7): 491 - 498.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
H. W. H. G. Kessels, A. C. Ward, and T. N. M. Schumacher
Specificity and affinity motifs for Grb2 SH2-ligand interactions
PNAS, June 25, 2002; 99(13): 8524 - 8529.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. C. Pero, L. Oligino, R. J. Daly, A. L. Soden, C. Liu, P. P. Roller, P. Li, and D. N. Krag
Identification of Novel Non-phosphorylated Ligands, Which Bind Selectively to the SH2 Domain of Grb7
J. Biol. Chem., March 29, 2002; 277(14): 11918 - 11926.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
A. S. Mohamed, K. A. Rivas-Plata, J. R. Kraas, S. M. Saleh, and S. L. Swope
Src-Class Kinases Act within the Agrin/MuSK Pathway to Regulate Acetylcholine Receptor Phosphorylation, Cytoskeletal Anchoring, and Clustering
J. Neurosci., June 1, 2001; 21(11): 3806 - 3818.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
J. P. Northrop, D. Nguyen, S. Piplani, S. E. Olivan, S. T-S. Kwan, N. F. Go, C. P. Hart, and P. J. Schatz
Selection of Estrogen Receptor {beta}- and Thyroid Hormone Receptor {beta}-Specific Coactivator-Mimetic Peptides Using Recombinant Peptide Libraries
Mol. Endocrinol., May 1, 2000; 14(5): 605 - 622.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
S. H. Gee, S. A. Sekely, C. Lombardo, A. Kurakin, S. C. Froehner, and B. K. Kay
Cyclic Peptides as Non-carboxyl-terminal Ligands of Syntrophin PDZ Domains
J. Biol. Chem., August 21, 1998; 273(34): 21980 - 21987.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
L. Tong, T. C. Warren, S. Lukas, J. Schembri-King, R. Betageri, J. R. Proudfoot, and S. Jakes
Carboxymethyl-phenylalanine as a Replacement for Phosphotyrosine in SH2 Domain Binding
J. Biol. Chem., August 7, 1998; 273(32): 20238 - 20242.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. I. S. MacDonald, E. A. Gryz, C. J. Kubu, J. M. Verdi, and S. O. Meakin
Direct Binding of the Signaling Adapter Protein Grb2 to the Activation Loop Tyrosines on the Nerve Growth Factor Receptor Tyrosine Kinase, TrkA
J. Biol. Chem., June 9, 2000; 275(24): 18225 - 18233.
[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 © 1997 by the American Society for Biochemistry and Molecular Biology.