The X-linked lymphoproliferative-disease gene product SAP regulates signals induced through the co-receptor SLAM

@article{Sayos1998TheXL,
  title={The X-linked lymphoproliferative-disease gene product SAP regulates signals induced through the co-receptor SLAM},
  author={Joan Sayós and Chengbin Wu and Massimo Morra and Ninghai Wang and X. Zhang and Deborah J. Allen and Sandrijn M. van Schaik and Luigi Daniele Notarangelo and Raif S. Geha and Maria Grazia Roncarolo and Hans C. Oettgen and Jan E. de Vries and Gregorio Aversa and Cox Terhorst},
  journal={Nature},
  year={1998},
  volume={395},
  pages={462-469}
}
In addition to triggering the activation of B- or T-cell antigen receptors, the binding of a ligand to its receptor at the cell surface can sometimes determine the physiological outcome of interactions between antigen-presenting cells, T and B lymphocytes. The protein SLAM (also known as CDw150), which is present on the surface of B and T cells, forms such a receptor–ligand pair as it is a self-ligand. We now show that a T-cell-specific, SLAM-associated protein (SAP), which contains an SH2… 

The X-linked lymphoproliferative disease gene product SAP associates with PAK-interacting exchange factor and participates in T cell activation

TLDR
It is reported that in T cells, SAP associates with the PAK-interacting exchange factor (PIX), a guanine nucleotide exchange factor specific for Rac/Cdc42 GTPases and it is shown that SAP is required for the recruitment of PIX to the SLAM-family receptors.

The SAP and SLAM families in immune responses and X-linked lymphoproliferative disease

TLDR
This review discusses recent findings on the structure and function of proteins of the SAP and SLAM families and considers how these proteins control signal transduction that is initiated by SLAM-related receptors in professional antigen-presenting cells.

Regulation of SLAM-mediated signal transduction by SAP, the X-linked lymphoproliferative gene product

TLDR
It is shown that signaling via the SLAM-SAP pathway in an established T cell line can alter the profile of cytokine production during T cell activation, and a mechanism by which a putative adaptor molecule is required for receptor-mediated signaling events in the immune system is identified.

The Adaptor Protein SAP Directly Associates with CD3ζ Chain and Regulates T Cell Receptor Signaling

TLDR
It is shown that SAP plays a central function in the T cell activation processes through a direct association with the CD3 complex through the first ITAM of CD3ζ, proximal to the membrane.

Cell surface receptors Ly-9 and CD84 recruit the X-linked lymphoproliferative disease gene product SAP.

TLDR
It is concluded that in activated T cells, the SAP protein binds to and regulates signal transduction events initiated through the engagement of SLAM, 2B4, CD84, and Ly-9, which suggests that combinations of dysfunctional signaling pathways initiated by these 4 cell surface receptors may cause the complex phenotypes of XLP.

Role of SLAM-Associated Protein in the Pathogenesis of Autoimmune Diseases and Immunological Disorders

TLDR
The role of SAP-mediated signaling in the induction of autoimmune diseases has been analyzed using animal models such as lupus, hepatitis, and graft-versus-host disease and is considered important in their pathogenesis in humans.

Molecular and immunological basis of X‐linked lymphoproliferative disease

TLDR
Functional and genetic analyses suggest that the phenotype associated with XLP is caused in large part by defects in the functions of SLAM‐related receptors due to SAP deficiency.

Dual Functional Roles for the X-linked Lymphoproliferative Syndrome Gene Product SAP/SH2D1A in Signaling through the Signaling Lymphocyte Activation Molecule (SLAM) Family of Immune Receptors*

TLDR
It is demonstrated that SAP binds with comparable affinities to the same sites in these receptors as do the SH2 domains of SHP-2 and SHIP, suggesting that these three proteins may compete against one another in binding to a given SLAM family receptor.
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