Disease relevance of SLAMF1

• Measles virus uses CD150 as a receptor and Molluscum contagiosum virus encodes proteins that are homologous to CD150 [1].
• CD150 signaling lymphocytic activation molecule (SLAM), a T/B/dendritic cell surface glycoprotein, is a costimulatory receptor involved in T-cell activation and is also a receptor for measles virus [2].
• Analysis of CD150 and SH2D1A expression in non-Hodgkin and Hodgkin lymphomas revealed stages of B-cell differentiation where these molecules are expressed alone or coexpressed [3].
• Signaling studies in Hodgkin disease cell lines showed that CD150 is linked to the ERK and Akt pathways in neoplastic B cells [3].
• Surprisingly, the CD4-8- thymocytes of CD3gammadeltanull mice, but not of Ragnull or severe combined immunodeficiency mice, expressed CD150 [4].

High impact information on SLAMF1

• Here we show that human SLAM (signalling lymphocyte-activation molecule; also known as CDw150), a recently discovered membrane glycoprotein expressed on some T and B cells, is a cellular receptor for measles virus, including the Edmonston strain [5].
• 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 [6].
• Consistent with its single src homology 2 (SH2) domain architecture and unusually high affinity for SLAM (also called CD150), SAP has been suggested to function by blocking binding of SHP-2 or other SH2-containing signalling proteins to SLAM receptors [7].
• The T and natural killer (NK) cell-specific gene SAP (SH2D1A) encodes a 'free SH2 domain' that binds a specific tyrosine motif in the cytoplasmic tail of SLAM (CD150) and related cell surface proteins [8].
• Here we show that the signaling pathways triggered during platelet aggregation include an intrinsic pro-thrombotic activity mediated by 2 homophilic adhesion molecules, CD84 and CD150 (SLAM [signaling lymphocyte activation molecule]), which are tyrosine phosphorylated in a platelet aggregation-dependent fashion [9].

Chemical compound and disease context of SLAMF1

• Histidine at position 61 and its adjacent amino acid residues are critical for the ability of SLAM (CD150) to act as a cellular receptor for measles virus [10].

Biological context of SLAMF1

• Characteristically, the SH2D1A three-pronged interaction with Tyr(281) of CD150 can occur in absence of phosphorylation [11].
• To analyze CD150-initiated signal transduction pathways, we used DT40 B-cell sublines deficient in these molecules [3].
• The ability of CDw150 to regulate cell death does not correlate with serine phosphorylation of the Akt kinase, but does correlate with SHIP tyrosine dephosphorylation [12].
• CDw150 associates with src-homology 2-containing inositol phosphatase and modulates CD95-mediated apoptosis [12].
• Mechanism of CD150 (SLAM) down regulation from the host cell surface by measles virus hemagglutinin protein [13].

Anatomical context of SLAMF1

• Here we report that SH2D1A is expressed in tonsillar B cells and in some B lymphoblastoid cell lines, where CD150 coprecipitates with SH2D1A and SHIP [14].
• The CD150 receptor is expressed on activated T and B lymphocytes, dendritic cells, and monocytes [3].
• The CD150 (SLAM) family consists of nine leukocyte cell-surface proteins involved in lymphocyte activation that belong to the immunoglobulin (Ig) superfamily [15].
• CD84 and CD150 were present on thymocytes, mature T cells and antigen-presenting cells [15].
• Next, we showed that DCs that matured via stimulation of their Toll-like receptors (TLRs) 2 and/or 4 exhibited an approximately fivefold increase in CDw150 at the protein level, and concomitantly, higher levels of MV amplification were observed in mixed culture of lymphocytes than in iDCs without TLR2/4 stimuli [16].

Associations of SLAMF1 with chemical compounds

• The EAT-2 structure in complex with a phosphotyrosine peptide containing a sequence motif with Tyr281 of the cytoplasmic tail of CD150 is very similar to the structure of SH2D1A complexed with the same peptide [8].
• A TxYxxV/I motif in the CD150 cytoplasmic tail can bind different SH2-containing molecules, including tyrosine and inositol phosphatases, Src family kinases, and adaptor molecules [3].
• A leucine residue, Leu278, further stabilizes nonphospho binding of SAP to Tyr281 of CD150 [2].
• Human signalling lymphocyte activation molecule (SLAM; also called CD150), a membrane glycoprotein of the immunoglobulin superfamily, acts as a cellular receptor for MV [17].

Regulatory relationships of SLAMF1

• CD150 association with either the SH2-containing inositol phosphatase or the SH2-containing protein tyrosine phosphatase is regulated by the adaptor protein SH2D1A [14].
• All CD-VLPs formed syncytia after infection in CHO cells expressing CD150 but not in those expressing CD46 [18].
• Notably, an alternative MV receptor SLAM CDw150 was neither expressed nor recruited to this complex throughout GM-CSF-mediated Mphi differentiation [19].

Other interactions of SLAMF1

• Using GST-fusion proteins with single replacements of tyrosine at Y269F, Y281F, Y307F, or Y327F in the CD150 cytoplasmic tail, we found that the same phosphorylated Y281 and Y327 are essential for both SHP-2 and SHIP binding [14].
• In contrast to CD84, CD150 was absent on resting monocytes and immature dendritic cells (DCs) [15].
• Strikingly, CDw150 was not detected in monocytes and moderately induced in iDCs, while CD46 was constantly expressed in monocyte-to-iDC differentiation [16].
• DSHP binds to the cytoplasmic domains of CDw150 (Signaling Lymphocyte Activation Molecule, SLAM) and 2B4, and may regulate signals transmitted by these receptors in T and NK cells, respectively [20].
• TLR-mediated functional potential of DCs may affect the degree of MV amplification through distinct MV strain-specific receptor usage of CDw150 or CD46 [16].

Analytical, diagnostic and therapeutic context of SLAMF1

• Molecular dissection of the signaling and costimulatory functions of CD150 (SLAM): CD150/SAP binding and CD150-mediated costimulation [2].
• Ligation of CDw150 induces the rapid dephosphorylation of both SHIP and CDw150 as well as the association of Lyn and Fgr with SHIP [12].
• To better evaluate the role of hSLAM in MV pathogenesis and MV-induced immunosuppression, we created transgenic (tg) mice that expressed the hSLAM molecule under the control of the lck proximal promoter. hSLAM was expressed on CD4(+) and CD8(+) T cells in the blood and spleen and also on CD4(+), CD8(+), CD4(+) CD8(+), and CD4(-) CD8(-) thymocytes [21].
• METHODS: The expression of CD150 splicing forms and SH2D1A adaptor protein in HD primary lymphoma tissue and cell lines were analyzed by RT-PCR method [22].

References