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

  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},
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

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

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

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

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.

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

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

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*

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.



A novel receptor involved in T-cell activation

SLAM is a novel receptor on T cells that, when engaged, potentiates T-cell expansion in a CD28-independent manner and induces a ThO/Thl cytokine production profile.

SLAM and its role in T cell activation and Th cell responses

SLAM is discussed as a receptor involved in T cell expansion and in directing immune responses to a Th0‐Th 1 pathway and was found to be a high‐affinity self‐ligand mediating molecular and cellular homophilic interactions.

X-Linked Lymphoproliferative Disease: Twenty-Five Years after the Discovery

The X-linked lymphoproliferative disease (XLP), one of six described X-linked immunodeficiencies, stems from a mutation at Xq25 which renders males impotent to mount an effective immune response to

Engagement of the signaling lymphocytic activation molecule (SLAM) on activated T cells results in IL-2-independent, cyclosporin A-sensitive T cell proliferation and IFN-gamma production.

SLAM is a novel receptor that mediates IL-2-independent expansion of activated T cells during immune responses, while concomitantly directing these proliferating cells to a Th0/Th1 pathway, whereas stimulation via SLAM reverses the cytokine production profile of Th2 clones to aTh0 phenotype, whereas it further polarizes cytokineProduction by Th1 clones.

Blockade of T-cell activation by dithiocarbamates involves novel mechanisms of inhibition of nuclear factor of activated T cells

The activation of an NFAT kinase by PDTC could be responsible for the rapid shuttling of the NFAT, therefore transiently converting the sustained transactivation of this transcription factor that occurs during lymphocyte activation, and c-Jun NH2-terminal kinase (JNK) can act by directly phosphorylating NFATp.

Soluble and Membrane-bound Forms of Signaling Lymphocytic Activation Molecule (SLAM) Induce Proliferation and Ig Synthesis by Activated Human B Lymphocytes

In this study it is shown that both membrane-bound and soluble forms of signaling lymphocytic activation molecule (SLAM) induce proliferation and Ig synthesis by activated human B cells. Activated B

Tyrosine Phosphorylation of the CD3-ε Subunit of the T Cell Antigen Receptor Mediates Enhanced Association with Phosphatidylinositol 3-Kinase in Jurkat T Cells*

It is demonstrated that tyrosine phosphorylation of CD3-ε can recruit the PI 3-kinase enzyme in a T cell activation-dependent manner, and this data support a model in which a single CD3 subunit can recruit distinct effector molecules by means of TCR-mediated differential ITAMosphorylation.

Immunopathology of the X-linked lymphoproliferative syndrome.

  • D. Purtilo
  • Biology, Medicine
    Haematology and blood transfusion
  • 1981

Regulation of T Cell Receptor Signaling by Tyrosine Phosphatase SYP Association with CTLA-4

The absence of CTLA-4 results in uncontrolled T cell proliferation. The T cell receptor-specific kinases FYN, LCK, and ZAP-70 as well as the RAS pathway were found to be activated in T cells of

WIP, a protein associated with wiskott-aldrich syndrome protein, induces actin polymerization and redistribution in lymphoid cells.

It is suggested that WIP plays a role in cortical actin assembly that may be important for lymphocyte function and is identified using the yeast two-hybrid system.