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Sci. STKE, 7 August 2001
Vol. 2001, Issue 94, p. tw1
[DOI: 10.1126/stke.2001.94.tw1]


Immunology SAP Orchestrates SLAM Signals

The activation of immune cells requires tight control of signaling. Signaling through the signaling lymphocyte activation molecule (SLAM) attenuates T cell stimulation, and mutation of the SLAM-associated protein (SAP) results in X-linked lymphoproliferative (XLP) disease. Latour et al. have identified some of the components required for SLAM signaling and have found that SAP mediates the formation of a protein complex on SLAM. SAP consists of little more than a single src homology 2 (SH2) domain, yet Latour et al. found that phosphotyrosine-independent binding of SAP to the plasma membrane-proximal Tyr288 of SLAM led to the recruitment of the protein tyrosine kinase FynT to SLAM. Tyr315 and Tyr335 both underwent phosphorylation and recruited the adaptor proteins Shc, Dok1 and Dok2, the SH2 domain-containing inositol phosphatase (SHIP), and RasGAP. Activated SLAM, in the presence of SAP, blocked the secretion of the T helper cell type 1 (Th1) cytokine interferon-{gamma} (IFN-{gamma}), but not interleukin-2 from T cell receptor-stimulated T cells in vitro. Upon T cell activation, the amount of cellular SAP decreases, whereas the amount of SLAM increases slightly. Subsequently, the amount of SAP increases, which leads to decreased IFN-{gamma} output. Thus, these results suggest that SLAM and SAP might act to fine-tune the profile of cytokines produced over the duration of the immune response.

S. Latour, G. Gish, C. D. Helgason, R. K. Humphries, T. Pawson, A. Veillette, Regulation of SLAM-mediated signal transduction by SAP, the X-linked lymphoproliferative gene product. Nature Immunol. 2, 681-690 (2001). [Online Journal]

Citation: SAP Orchestrates SLAM Signals. Sci. STKE 2001, tw1 (2001).

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