Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Sci. Signal., 4 May 2010
Vol. 3, Issue 120, p. ra34
[DOI: 10.1126/scisignal.2000796]


Editor's Summary

Picking the Right Partner
Proteins often interact through motifs or protein domains. Although a particular class of domains generally recognizes a similar motif in their partners, such as the SH2 domain that recognizes proteins containing phosphorylated tyrosine residues, individual members of the domain family also exhibit specificity. Phosphorylation of tyrosine residues is involved in many cell regulatory processes, and particular SH2 domain–containing proteins interact with specific partner proteins upon their phosphorylation. Kaneko et al. address the question of how a particular SH2 domain knows to which phosphorylated tyrosine–containing protein it should bind. In other words, how do the structurally similar SH2 domains exhibit selectivity for particular sequences even though they all contain phosphorylated tyrosine? By examining crystal and solution structures, the authors found that, in addition to a binding pocket for the phosphorylated tyrosine, SH2 domains had three other binding pockets and that loops, which are variable regions of the SH2 domain, controlled the accessibility of these other binding pockets to specify selectivity. With information about the rules governing binding pocket accessibility, the authors switched SH2 domain specificity by engineering key mutations into the loops. Not only does their work suggest a paradigm for understanding the origin of SH2 domain specificity, it also shows that specificity can be engineered, which may be important for rational design of SH2-specific inhibitors and antibodies.

Citation: T. Kaneko, H. Huang, B. Zhao, L. Li, H. Liu, C. K. Voss, C. Wu, M. R. Schiller, S. S. C. Li, Loops Govern SH2 Domain Specificity by Controlling Access to Binding Pockets. Sci. Signal. 3, ra34 (2010).

Read the Full Text

Specificity of Linear Motifs That Bind to a Common Mitogen-Activated Protein Kinase Docking Groove.
A. Garai, A. Zeke, G. Gogl, I. Toro, F. Fordos, H. Blankenburg, T. Barkai, J. Varga, A. Alexa, D. Emig, et al. (2012)
Science Signaling 5, ra74
   Abstract »    Full Text »    PDF »
Superbinder SH2 Domains Act as Antagonists of Cell Signaling.
T. Kaneko, H. Huang, X. Cao, X. Li, C. Li, C. Voss, S. S. Sidhu, and S. S. C. Li (2012)
Science Signaling 5, ra68
   Abstract »    Full Text »    PDF »
Evolution of SH2 domains and phosphotyrosine signalling networks.
B. A. Liu and P. D. Nash (2012)
Phil Trans R Soc B 367, 2556-2573
   Abstract »    Full Text »    PDF »
Two Closely Spaced Tyrosines Regulate NFAT Signaling in B Cells via Syk Association with Vav.
C.-H. Chen, V. A. Martin, N. M. Gorenstein, R. L. Geahlen, and C. B. Post (2011)
Mol. Cell. Biol. 31, 2984-2996
   Abstract »    Full Text »    PDF »
Mechanism of Phosphorylation-induced Activation of Phospholipase C-{gamma} Isozymes.
A. Gresset, S. N. Hicks, T. K. Harden, and J. Sondek (2010)
J. Biol. Chem. 285, 35836-35847
   Abstract »    Full Text »    PDF »
Signals: Tinkering with Domains.
E. Bornberg-Bauer (2010)
Science Signaling 3, pe31
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882