SLAMF1
Description
The SLAMF1 (signaling lymphocytic activation molecule family member 1) is a protein-coding gene located on chromosome 1.
Signaling lymphocytic activation molecule 1 is a protein that in humans is encoded by the SLAMF1 gene. Recently SLAMF1 has also been designated CD150 (cluster of differentiation 150). SLAMF1 belongs to the signaling lymphocytic activation molecule family. As other receptors from this family, SLAMF1 is expressed in different types of hematopoietic cells and it plays a role in the regulation of the immune system.
== Gene == The gene encoding SLAMF1 receptor is located on the human chromosome 1. It consists of eight exons and seven introns. Alternative splicing of SLAMF1 transcripts results in several isoforms of the protein, including the conventional transmembrane isoform (mCD150), secreted isoform (sCD150) cytoplasmic isoform (cCD150), and the novel transmembrane isoform (nCD150). SLAMF1 is expressed in hematopoietic stem cells. It is also used as one of the markers for their identification. Furthermore, its expression was detected in thymocytes, NKT cells, T cells, B cells, monocytes, macrophages and dendritic cells.
SLAMF1, also known as CD150, is a self-ligand receptor belonging to the signaling lymphocytic activation molecule (SLAM) family. It plays a crucial role in regulating and interconnecting both innate and adaptive immune responses by modulating the activation and differentiation of various immune cells. Its activity is controlled by the presence or absence of small cytoplasmic adapter proteins, SH2D1A/SAP and/or SH2D1B/EAT-2. The signaling pathways triggered by SLAMF1 in T-lymphocytes and B-cells differ. Two main signaling modes have been identified: one relying on SH2D1A (and possibly SH2D1B) and another dependent on protein-tyrosine phosphatase 2C (PTPN11). It was initially suggested that SH2D1A association prevents binding to inhibitory effectors like INPP5D/SHIP1 and PTPN11/SHP-2. However, SH2D1A also regulates signaling by interacting with and recruiting FYN, which subsequently phosphorylates and activates SLAMF1. SLAMF1 mediates IL-2-independent proliferation of activated T-cells during immune responses and induces IFN-gamma production. Downstream signaling involving INPP5D, DOK1, and DOK2 inhibits IFN-gamma production in T-cells, while PRKCQ, BCL10, and NFKB1 lead to increased T-cell activation and Th2 cytokine production. SLAMF1 promotes T-cell receptor-induced IL-4 secretion by CD4(+) cells and inhibits antigen receptor-mediated IFN-gamma production (but not IL-2) in CD4(-)/CD8(-) T-cells. It is required for IL-4 production by germinal center T follicular helper (T(Fh)) cells. SLAMF1 may inhibit CD40-induced signal transduction in monocyte-derived dendritic cells. It might play a role in allergic responses and regulate allergen-induced Th2 and Th1 cytokine secretion. In conjunction with SLAMF6, SLAMF1 controls the transition between positive selection and the subsequent expansion and differentiation of the thymocytic natural killer T (NKT) cell lineage. It is involved in the peripheral differentiation of indifferent natural killer T (iNKT) cells toward a regulatory NKT2 type. In macrophages, SLAMF1 participates in the down-regulation of IL-12, TNF-alpha, and nitric oxide in response to lipopolysaccharide (LPS). In B-cells, SLAMF1 activates the ERK signaling pathway independently of SH2D1A but involving both SYK and INPP5D. It also activates Akt signaling dependent on SYK and SH2D1A. Additionally, it activates p38 MAPK and JNK1 and JNK2 in B-cells. Along with CD84/SLAMF5 and SLAMF6, SLAMF1 might act as a negative regulator of the humoral immune response. SLAMF1 is involved in the innate immune response against Gram-negative bacteria in macrophages. It likely recognizes OmpC and/or OmpF on the bacterial surface, regulates phagosome maturation and recruitment of the PI3K complex II (PI3KC3-C2), leading to PdtIns(3)P accumulation and NOX2 activity in the phagosomes. SLAMF1 functions as a receptor for Measles virus, including isoform 4. It interacts with SH2D1A and SH2D1B via its cytoplasmic domain. SH2D1A mediates association with FYN and binds to both phosphorylated and non-phosphorylated ITSM 1. Through its cytoplasmic domain, phosphorylated on tyrosine residues, SLAMF1 interacts with INPP5D and PTPN11, with SH2D1A facilitating binding to INPP5D. It also interacts with MAP4K1, PIK3C3, BECN1, and UVRAG, suggesting an association with PI3K complex II (PI3KC3-C2). Finally, SLAMF1 interacts with measles hemagglutinin protein.
SLAMF1 is also known as CD150, CDw150, SLAM.
