Signaling lymphocytic activation molecule

[3] SLAMs have a variety of functions, including enhancing T cellular proliferation by stimulating IL-4 and IFN-gamma production.

[4] SLAM family (SLAMF) receptors can interact directly with microbes, which can cause phagocytic cells to migrate to the area.

[11][4] The IgV and IgC2 domains are located on the extracellular portion of the receptor, while the ITSMs are used for signaling within the cell.

[13] The X-linked SLAM-associated protein (SAP), encoded by the SH2D1A gene, consists primarily of an SH2 domain which can interact with ITSMs present on most SLAMF receptors.

[4][3] A defective SLAM associated protein (SAP) causes X-linked lymphoproliferative syndrome (XLP), a frequently lethal mononucleosis characterized by inability to respond to infection with Epstein-Barr virus (EBV), leading to a failure to clear B-cells infected with the virus, which can be fatal.

This diagram shows the signaling pathway for a SLAMF1 receptor in a CD4 T-helper cell. It depicts SAP (Slam-Associated Protein) outcompeting EAT-2 (Ewing’s sarcoma-associated transcript 2) using a 3-pronged binding pattern to ITSMs on the SLAMF. The ITSMs do not necessarily need to be phosphorylated for SAP to bind, but they do need to be phosphorylated for EAT-2 to bind. SAP binding leads to Fyn recruitment and eventually IL-4 and IFN-gamma release.