SLAMF7 Antibody - #DF14380

Self-ligand receptor of the signaling lymphocytic activation molecule (SLAM) family. SLAM receptors triggered by homo- or heterotypic cell-cell interactions are modulating the activation and differentiation of a wide variety of immune cells and thus are involved in the regulation and interconnection of both innate and adaptive immune response. Activities are controlled by presence or absence of small cytoplasmic adapter proteins, SH2D1A/SAP and/or SH2D1B/EAT-2. Isoform 1 mediates NK cell activation through a SH2D1A-independent extracellular signal-regulated ERK-mediated pathway. Positively regulates NK cell functions by a mechanism dependent on phosphorylated SH2D1B. Downstream signaling implicates PLCG1, PLCG2 and PI3K. In addition to heterotypic NK cells-target cells interactions also homotypic interactions between NK cells may contribute to activation. However, in the absence of SH2D1B, inhibits NK cell function. Acts also inhibitory in T-cells (By similarity). May play a role in lymphocyte adhesion. In LPS-activated monocytes negatively regulates production of proinflammatory cytokines.

Isoform 3 does not mediate any NK cell activation.

Membrane>Single-pass type I membrane protein.

Expressed in spleen, lymph node, peripheral blood leukocytes, bone marrow, small intestine, stomach, appendix, lung and trachea. Expression was detected in NK cells, activated B-cells, NK-cell line but not in promyelocytic, B-, or T-cell lines. Expressed in monocytes. Isoform 3 is expressed at much lower level than isoform 1.

Isoform 1 binds to SH2D1A when its cytoplasmic tail is phosphorylated in the presence of FYN (in vitro); low affinity binding, the physiological relevance of the interaction is questioned. Interacts with SH2D1B; in NK cells. Interacts (via ITSM phosphorylated on Tyr-302) with SH2D1B, PTPN6/SHP-1, PTPN11/SHP-2, INPP5D/SHIP1, CSK and FYN (By similarity).

The ITSMs (immunoreceptor tyrosine-based switch motifs) with the consensus sequence T-X-Y-X-X-[VI] present in SLAM family receptors have overlapping specificity for activating and inhibitory SH2 domain-containing binding partners. Especially they mediate the interaction with the SH2 domain of SH2D1A and SH2D1B. A 'three-pronged' mechanism is proposed involving threonine (position -2), phosphorylated tyrosine (position 0) and valine/isoleucine (position +3).