SLAMF1

Last updated
SLAMF1
PDB 1d4t EBI.jpg
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases SLAMF1 , CD150, CDw150, SLAM, signaling lymphocytic activation molecule family member 1
External IDs OMIM: 603492 MGI: 1351314 HomoloGene: 48162 GeneCards: SLAMF1
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_003037
NM_001330754

NM_013730
NM_001360898

RefSeq (protein)

NP_001317683
NP_003028

NP_038758
NP_001347827

Location (UCSC) Chr 1: 160.61 – 160.65 Mb Chr 1: 171.59 – 171.63 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Signaling lymphocytic activation molecule 1 is a protein that in humans is encoded by the SLAMF1 gene. [5] [6] Recently SLAMF1 has also been designated CD150 (cluster of differentiation 150).

Contents

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. [7]

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). [7]

SLAMF1 is expressed in hematopoietic stem cells. It is also used as one of the markers for their identification. [8] Furthermore, its expression was detected in thymocytes, NKT cells, T cells, B cells, monocytes, macrophages and dendritic cells. Monocytes, macrophages and dendritic cells express SLAMF1 after their activation. The activation of T cells and plasma cell differentiation leads to the increased expression of this receptor. [7] [8] The interaction of SLAMF1 promoter and enhancers with the Early B-cell factor 1 (EBF1) is required for the expression of SLAMF1 gene in B cells. STAT6, IRF4, and NF-kB factors involved in the transfer of the signals from the B-cell receptor, its co-receptors and IL-4R, also play important role in the regulation of SLAMF1 expression. [9] The expression of SLAMF1 is not restricted to immune cells and their progenitors. From non-immune cells, platelets express SLAMF1. [7] [8]

Structure

SLAMF1 is a type I transmembrane protein belonging to the immunoglobulin superfamily. [8] Its molecular weight is between 70 kDa and 95 kDa. The extracellular region of the receptor is composed of one Ig variable-like domain and one Ig constant 2-like domain. The intracellular region of the receptor contains two intracellular tyrosine-based switch motives (ITSMs) that interact with SH2 domain-containing proteins. However, nCD150 intracellular region differs from other isoforms of this protein, it lacks ITSMs. sCD150 isoform lacks the transmembrane domain and therefore, it can not be anchored to the cell membrane. [7]

Signaling

The receptor SLAMF1 mediates homophilic interactions as most of the receptors from the SLAMF. Signaling from SLAMF1 receptor can be activating or inhibitory. The type of the signal depends on the cell type, differentiation stage, and the combination of signals from other receptors. [7]

SH2 domain-containing proteins, specifically adaptor proteins SAP and EAT-2, and phosphatases SHP-1, SHP-2 and SHIP, interact with ITSMs in the intracellular region of SLAMF1. [7] [10] Binding of SAP to ITSMs leads to the activation of the kinase Fyn that phosphorylates tyrosines of SLAMF1 and recruits downstream signaling proteins. Because of the high affinity of SAP to tyrosine phosphorylated ITSMs, it outcompetes the phosphatases which are the mediators of the inhibitory signal. Therefore, the expression and availability of SAP play a crucial role in the determination of the type of the signal. [11] [12]

Function

SLAMF1 is involved in the regulation of thymocyte development, T cell proliferation, differentiation and T cell function, such as the cytotoxic activity of CD8+ T cells and the production of IL-4, IL-13 and IFNγ. In B cells, it regulates the proliferation and the antibody production. [7] [8] SLAMF1 acts as a self-ligand during the interaction between B cells and T cells and promotes lymphocyte activation. [10]

The development of NKT cells is dependent on a signal mediated by SAP. It was found out that the homophilic interaction of SLAMF1 or SLAMF6 is required for SAP recruitment in NKT cells. This interaction mediates a secondary signal crucial for NKT cell differentiation and expansion in the thymus. [13]

SLAMF1 expression in macrophages is associated with killing of Gram-negative bacteria. SLAMF1 acts as a bacterial sensor. It is internalized after the recognition of Gram-negative bacteria, and it plays a role in the regulation of phagosome maturation, ROS and NO production. The absence of SLAMF1 in phagocytes leads, among other things, to the disruption of cytokine production. [13]

Role of SLAMF1 in diseases

Viral infections

SLAMF1 is a receptor for Morbilliviruses. [7] This genus of viruses includes agents causing measles in humans, rinderpest in cattle and distemper in dogs and cats. [14] Ig variable-like domain of SLAMF1 binds to hemagglutinin on the surface of the virus and this interaction mediates the virus entry into the host cell. [7]

Cancer

SLAMF1 is expressed in cancer cells in some types of hematologic malignancies (cutaneous T-cell lymphoma, few types of B-cell non-Hodgkin´s lymphoma, Hodgkin´s lymphoma and about 50 % of chronic lymphocytic leukemia cases). [7] It regulates cancer cell growth and survival by activating PI3K/Akt/mTOR signaling pathway. Therefore, SLAMF1 could be used as a diagnostical and prognostic marker in these cancer types. [8] Several cases of leukemia or Hodgkin´s lymphoma remission after measles virus infection or vaccination have been described. Therefore, SLAMF1 could be used as a target for cancer therapy which is based on the measles virus-mediated lysis of the cancer cells. [7]

nCD150 isoform was found in tumors of the central nervous system, such as glioblastoma, anaplastic and diffuse astrocytoma and ependymoma. [10]

Related Research Articles

<i>Measles morbillivirus</i> Species of virus

Measles morbillivirus(MeV), also called measles virus (MV), is a single-stranded, negative-sense, enveloped, non-segmented RNA virus of the genus Morbillivirus within the family Paramyxoviridae. It is the cause of measles. Humans are the natural hosts of the virus; no animal reservoirs are known to exist.

<span class="mw-page-title-main">CD40 (protein)</span> Mammalian protein found in Homo sapiens

Cluster of differentiation 40, CD40 is a type I transmembrane protein found on antigen-presenting cells and is required for their activation. The binding of CD154 (CD40L) on TH cells to CD40 activates antigen presenting cells and induces a variety of downstream effects.

<span class="mw-page-title-main">Antigen presentation</span> Vital immune process that is essential for T cell immune response triggering

Antigen presentation is a vital immune process that is essential for T cell immune response triggering. Because T cells recognize only fragmented antigens displayed on cell surfaces, antigen processing must occur before the antigen fragment can be recognized by a T-cell receptor. Specifically, the fragment, bound to the major histocompatibility complex (MHC), is transported to the surface of the cell, a process known as presentation. If there has been an infection with viruses or bacteria, the cell will present an endogenous or exogenous peptide fragment derived from the antigen by MHC molecules. There are two types of MHC molecules which differ in the behaviour of the antigens: MHC class I molecules (MHC-I) bind peptides from the cell cytosol, while peptides generated in the endocytic vesicles after internalisation are bound to MHC class II (MHC-II). Cellular membranes separate these two cellular environments - intracellular and extracellular. Each T cell can only recognize tens to hundreds of copies of a unique sequence of a single peptide among thousands of other peptides presented on the same cell, because an MHC molecule in one cell can bind to quite a large range of peptides. Predicting which antigens will be presented to the immune system by a certain MHC/HLA type is difficult, but the technology involved is improving.

<span class="mw-page-title-main">CD80</span> Mammalian protein found in Homo sapiens

The Cluster of differentiation 80 is a B7, type I membrane protein in the immunoglobulin superfamily, with an extracellular immunoglobulin constant-like domain and a variable-like domain required for receptor binding. It is closely related to CD86, another B7 protein (B7-2), and often works in tandem. Both CD80 and CD86 interact with costimulatory receptors CD28, CTLA-4 (CD152) and the p75 neurotrophin receptor.

<span class="mw-page-title-main">CD86</span> Mammalian protein found in Homo sapiens

Cluster of Differentiation 86 is a protein constitutively expressed on dendritic cells, Langerhans cells, macrophages, B-cells, and on other antigen-presenting cells. Along with CD80, CD86 provides costimulatory signals necessary for T cell activation and survival. Depending on the ligand bound, CD86 can signal for self-regulation and cell-cell association, or for attenuation of regulation and cell-cell disassociation.

NKG2 also known as CD159 is a receptor for natural killer cells. There are 7 NKG2 types: A, B, C, D, E, F and H. NKG2D is an activating receptor on the NK cell surface. NKG2A dimerizes with CD94 to make an inhibitory receptor (CD94/NKG2).

<span class="mw-page-title-main">C-C chemokine receptor type 7</span> Protein-coding gene in the species Homo sapiens

C-C chemokine receptor type 7 is a protein that in humans is encoded by the CCR7 gene. Two ligands have been identified for this receptor: the chemokines ligand 19 (CCL19/ELC) and ligand 21 (CCL21). The ligands have similar affinity for the receptor, though CCL19 has been shown to induce internalisation of CCR7 and desensitisation of the cell to CCL19/CCL21 signals. CCR7 is a transmembrane protein with 7 transmembrane domains, which is coupled with heterotrimeric G proteins, which transduce the signal downstream through various signalling cascades. The main function of the receptor is to guide immune cells to immune organs by detecting specific chemokines, which these tissues secrete.

<span class="mw-page-title-main">SH2D1A</span> Protein-coding gene in the species Homo sapiens

SH2 domain–containing protein 1A is a protein that in humans is encoded by the SH2D1A gene. It is often called SLAM-associated protein, where "SLAM" refers to signaling lymphocytic activation molecules. It is a SH2 domain–containing molecule that plays a role in SLAM signaling. A putative function is as an adaptor for Fyn and competitor of phosphatases, leading to modulation of SLAM family function. SAP has been implicated in autoimmunity, and a mutation of it is associated with X-linked lymphoproliferative disease. At least 32 disease-causing mutations in this gene have been discovered.

<span class="mw-page-title-main">CD244</span> Protein found in humans

CD244 also known as 2B4 or SLAMF4 is a protein that in humans is encoded by the CD244 gene.

<span class="mw-page-title-main">NCR3</span> Mammalian protein found in Homo sapiens

Natural cytotoxicity triggering receptor 3 is a protein that in humans is encoded by the NCR3 gene. NCR3 has also been designated as CD337 and as NKp30. NCR3 belongs to the family of NCR membrane receptors together with NCR1 (NKp46) and NCR2 (NKp44).

<span class="mw-page-title-main">CD84</span> Protein found in humans

CD84 is a human protein encoded by the CD84 gene.

<span class="mw-page-title-main">CD226</span> Protein-coding gene in the species Homo sapiens

CD226, PTA1 or DNAM-1 is a ~65 kDa immunoglobulin-like transmembrane glycoprotein expressed on the surface of natural killer cells, NK T cell, B cells, dendritic cells, hematopoietic precursor cells, platelets, monocytes and T cells.

<span class="mw-page-title-main">SLAMF6</span> Protein-coding gene in humans

SLAM family member 6 is a protein that in humans is encoded by the SLAMF6 gene.

<span class="mw-page-title-main">BTLA</span> Protein-coding gene in the species Homo sapiens

B- and T-lymphocyte attenuator or BTLA is a protein that belongs to the CD28 immunoglobulin superfamily (IgSF) which is encoded by the BTLA gene located on the 3rd human chromosome. BTLA was first discovered in 2003 as an inhibitor of Th1 expansion and it became the 3rd member of the CD28 IgSF. However, its discovered ligand herpes virus entry mediator or HVEM belongs to the tumor necrosis factor receptor superfamily (TNFRSF). This finding was surprising because until the discovery of HVEM it was believed that receptors and ligands always belong to the same family.

<span class="mw-page-title-main">LY9</span> Protein-coding gene in humans

T-lymphocyte surface antigen Ly-9 is a protein that in humans is encoded by the LY9 gene. LY9 has also recently been designated CD229.

<span class="mw-page-title-main">CD200</span> Protein-coding gene in the species Homo sapiens

OX-2 membrane glycoprotein, also named CD200 is a human protein encoded by the CD200 gene. CD200 gene is in human located on chromosome 3 in proximity to genes encoding other B7 proteins CD80/CD86. In mice CD200 gene is on chromosome 16.

<span class="mw-page-title-main">FCGR2B</span>

Fc fragment of IgG receptor IIb is a low affinity inhibitory receptor for the Fc region of immunoglobulin gamma (IgG). FCGR2B participates in the phagocytosis of immune complexes and in the regulation of antibody production by B lymphocytes.

Signaling lymphocytic activation molecule (SLAM) is a family of genes. Homophilic binding between SLAMs is involved in cell-to-cell adhesion during antigen presentation.

X-linked lymphoproliferative disease is a lymphoproliferative disorder, usually caused by SH2DIA gene mutations in males. XLP-positive individuals experience immune system deficiencies that render them unable to effectively respond to the Epstein-Barr virus (EBV), a common virus in humans that typically induces mild symptoms or infectious mononucleosis (IM) in patients. There are two currently known variations of the disorder, known as XLP1 and XLP2. XLP1 is estimated to occur in approximately one in every million males, while XLP2 is rarer, estimated to occur in one of every five million males. Due to therapies such as chemotherapy and stem cell transplants, the survival rate of XLP1 has increased dramatically since its discovery in the 1970s.

<span class="mw-page-title-main">Paired receptors</span>

Paired receptors are pairs or clusters of receptor proteins that bind to extracellular ligands but have opposing activating and inhibitory signaling effects. Traditionally, paired receptors are defined as homologous pairs with similar extracellular domains and different cytoplasmic regions, whose genes are located together in the genome as part of the same gene cluster and which evolved through gene duplication. Homologous paired receptors often, but not always, have a shared ligand in common. More broadly, pairs of receptors have been identified that exhibit paired functional behavior - responding to a shared ligand with opposing intracellular signals - but are not closely homologous or co-located in the genome. Paired receptors are highly expressed in the cells of the immune system, especially natural killer (NK) and myeloid cells, and are involved in immune regulation.

References

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  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000015316 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Cocks BG, Chang CC, Carballido JM, Yssel H, de Vries JE, Aversa G (July 1995). "A novel receptor involved in T-cell activation". Nature. 376 (6537): 260–263. Bibcode:1995Natur.376..260C. doi:10.1038/376260a0. PMID   7617038. S2CID   4319295.
  6. "Entrez Gene: SLAMF1 signaling lymphocytic activation molecule family member 1".
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  8. 1 2 3 4 5 6 Farhangnia P, Ghomi SM, Mollazadehghomi S, Nickho H, Akbarpour M, Delbandi AA (2023-05-11). "SLAM-family receptors come of age as a potential molecular target in cancer immunotherapy". Frontiers in Immunology. 14: 1174138. doi: 10.3389/fimmu.2023.1174138 . PMC   10213746 . PMID   37251372.
  9. Schwartz AM, Putlyaeva LV, Covich M, Klepikova AV, Akulich KA, Vorontsov IE, et al. (October 2016). "Early B-cell factor 1 (EBF1) is critical for transcriptional control of SLAMF1 gene in human B cells". Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms. 1859 (10): 1259–1268. doi:10.1016/j.bbagrm.2016.07.004. PMID   27424222.
  10. 1 2 3 Fouquet G, Marcq I, Debuysscher V, Bayry J, Rabbind Singh A, Bengrine A, et al. (March 2018). "Signaling lymphocytic activation molecules Slam and cancers: friends or foes?". Oncotarget. 9 (22): 16248–16262. doi:10.18632/oncotarget.24575. PMC   5882332 . PMID   29662641.
  11. Dragovich MA, Mor A (July 2018). "The SLAM family receptors: Potential therapeutic targets for inflammatory and autoimmune diseases". Autoimmunity Reviews. 17 (7): 674–682. doi:10.1016/j.autrev.2018.01.018. PMC   6508580 . PMID   29729453.
  12. Wu N, Veillette A (February 2016). "SLAM family receptors in normal immunity and immune pathologies". Current Opinion in Immunology. 38: 45–51. doi:10.1016/j.coi.2015.11.003. PMID   26682762.
  13. 1 2 van Driel BJ, Liao G, Engel P, Terhorst C (2016-01-20). "Responses to Microbial Challenges by SLAMF Receptors". Frontiers in Immunology. 7: 4. doi: 10.3389/fimmu.2016.00004 . PMC   4718992 . PMID   26834746.
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Further reading