Editors' ChoiceInteraction Domains

The Versatile SH2 Domain

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Science's STKE  11 Feb 2003:
Vol. 2003, Issue 169, pp. tw69-TW69
DOI: 10.1126/stke.2003.169.tw69

Studies of an unusual adaptor protein that is essentially a single Src homology 2 domain have shown previously unrecognized versatility in interaction between SH2 and SH3 domains. The adaptor is known as SAP (SLAM-associated protein) and functions in T cells to promote signals from the receptor SLAM (signaling lymphocyte-activation molecule; also known as CDw150), which undergoes homotypic interactions with other SLAM molecules and is also the cellular receptor for measles virus. Loss of SAP causes human X-linked lymphoproliferative syndrome. SAP was first thought to work by competing with binding of other proteins that contain the SH2 domain. Now, however, Chan et al. and Latour et al. have shown that SAP binds to the SH3 domain of the tyrosine kinase FynT (the T cell isoform of Fyn) and activates the kinase. Chan et al. provide the crystal structure of a complex containing SLAM, SAP, and the SH3 domain of Fyn and reveal that the interaction is unlike canonical SH3 and SH2 interactions described in many other signaling proteins. The Fyn SH3 domain, for instance, appears unlikely to interact with a proline residue. The findings extend the functional interactions known for the SH2 and SH3 domains and suggest that similar interactions may occur through these domains in other signaling contexts.

S. Latour, R. Roncagalli, R. Chen, M. Bakinowski, X. Shi, P. L. Schwartzberg, D. Davidson, A. Veillette, Binding of SAP SH2 domain to FynT SH3 domain reveals a novel mechanism of receptor signalling in immune regulation. Nature Cell Biol. 5, 149-154 (2003). [Online Journal]

B. Chan, A. Lanyi, H. K. Song, J. Griesbach, M. Simarro-Grande, F. Poy, D. Howie, J. Sumegi, C. Terhorst, M. J. Eck, SAP couples Fyn to SLAM immune receptors. Nature Cell Biol. 5, 155-160 (2003). [Online Journal]

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