Seeking Alternative Pathways

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Science  21 May 2004:
Vol. 304, Issue 5674, pp. 1079
DOI: 10.1126/science.304.5674.1079b

Cell-surface receptors in the signaling lymphocyte activation molecule (SLAM) family play diverse roles in the lives of T and B lymphocytes, NK cells, dendritic cells, and macrophages. Members of this family use the adaptor protein SAP, which helps recruit other intracellular signaling proteins. Individuals with a mutation in SAP develop severe X-linked lymphoproliferative syndrome; similarly, deletion of SAP in mice leads to dysregulation of T helper type 2 (TH2) cell-mediated immunity.

Wang et al. examined the specific contribution of the SLAM pathway, versus that mediated by other SAP- associating proteins, by generating SLAM-deficient mice. The absence of SLAM signaling led to decreases in TH2 cell and macrophage function, affecting innate as well as adaptive immunity. Lee et al. observed that mice lacking the NK-specific inhibitory SLAM receptor 2B4 had augmented NK cell activity, suggesting that SAP-associating receptors can operate differently in different cell types, possibly as a result of differential expression of SAP or related adaptor proteins. — SJS

J. Exp. Med. 199, 1255; 1245 (2004).

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