Signaling lymphocytic activation molecule 1 is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that in humans is encoded by the ''SLAMF1''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

. Recently SLAMF1 has also been designated CD150 (

cluster of differentiation The cluster of differentiation (also known as cluster of designation or classification determinant and often abbreviated as CD) is a protocol used for the identification and investigation of cell surface molecules providing targets for immunophe ...

150). SLAMF1 belongs to the

signaling lymphocytic activation molecule Signaling lymphocytic activation molecule (SLAM) is a family of genes. Homophilic binding between SLAMs is involved in cell-to-cell adhesion during antigen presentation. Signaling lymphocytic activation molecules are a CD2-related surface rece ...

family. As other

receptors Receptor may refer to: *Sensory receptor, in physiology, any neurite structure that, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds ...

from this family, SLAMF1 is expressed in different types of

hematopoietic cells Haematopoiesis (; ; also hematopoiesis in American English, sometimes h(a)emopoiesis) is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells. In a healthy adult human, roughly ten b ...

and it plays a role in the regulation of the

immune system The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to bacteria, as well as Tumor immunology, cancer cells, Parasitic worm, parasitic ...

Gene

The

encoding SLAMF1

receptor Receptor may refer to: * Sensory receptor, in physiology, any neurite structure that, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and respond ...

is located on the human

chromosome 1 Chromosome 1 is the designation for the largest human chromosome. Humans have two copies of chromosome 1, as they do with all of the autosomes, which are the non-sex chromosomes. Chromosome 1 spans about 249 million nucleotide base pairs, which a ...

. It consists of eight

exons An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequence i ...

and seven

introns An intron is any Nucleic acid sequence, nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word ''intron'' is derived from the term ''intragenic region'', i.e., a region inside a gene."The notion of ...

Alternative splicing Alternative splicing, alternative RNA splicing, or differential splicing, is an alternative RNA splicing, splicing process during gene expression that allows a single gene to produce different splice variants. For example, some exons of a gene ma ...

of SLAMF1 transcripts results in several

isoforms A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene and are the result of genetic differences. While many perform the same or similar biological roles, some isoforms have uniqu ...

of the

, 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 Hematopoietic stem cells (HSCs) are the stem cells that give rise to other blood cells. This process is called haematopoiesis. In vertebrates, the first definitive HSCs arise from the ventral endothelial wall of the embryonic aorta within the ...

. It is also used as one of the markers for their identification. Furthermore, its expression was detected in

thymocytes A thymocyte is an immune cell present in the thymus, before it undergoes transformation into a T cell. Thymocytes are produced as stem cells in the bone marrow and reach the thymus via the blood. Thymopoiesis describes the process which turns thym ...

, NKT cells,

T cells T cells (also known as T lymphocytes) are an important part of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their ce ...

B cells B cells, also known as B lymphocytes, are a type of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or inserted into the plasm ...

monocytes Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and monocyte-derived dendritic cells. As a part of the vertebrate innate immune system monocytes also i ...

macrophages Macrophages (; abbreviated MPhi, φ, MΦ or MP) are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that ...

and

dendritic cells A dendritic cell (DC) is an antigen-presenting cell (also known as an ''accessory cell'') of the mammalian immune system. A DC's main function is to process antigen material and present it on the cell surface to the T cells of the immune system ...

Monocytes Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and monocyte-derived dendritic cells. As a part of the vertebrate innate immune system monocytes also i ...

and

express SLAMF1 after their activation. The activation of

and

plasma cell Plasma cells, also called plasma B cells or effector B cells, are white blood cells that originate in the lymphoid organs as B cells and secrete large quantities of proteins called antibodies in response to being presented specific substances ca ...

differentiation leads to the increased expression of this

. The interaction of SLAMF1 promoter and

enhancers In genetics, an enhancer is a short (50–1500 bp) region of DNA that can be bound by proteins ( activators) to increase the likelihood that transcription of a particular gene will occur. These proteins are usually referred to as transcriptio ...

with the Early B-cell factor 1 (EBF1) is required for the expression of SLAMF1 gene in

STAT6 Signal transducer and activator of transcription 6 (STAT6) is a transcription factor that belongs to the Signal Transducer and Activator of Transcription (STAT) family of proteins. The proteins of STAT family transmit signals from a receptor c ...

IRF4 Interferon regulatory factor 4 (IRF4) also known as MUM1 is a protein that in humans is encoded by the ''IRF4'' gene. IRF4 functions as a key regulatory transcription factor in the development of human immune cells.Nam S, Lim J-S (2016). "Essentia ...

, and NF-kB factors involved in the transfer of the signals from the

B-cell receptor The B-cell receptor (BCR) is a transmembrane protein on the surface of a B cell. A B-cell receptor is composed of a membrane-bound immunoglobulin molecule and a signal transduction moiety. The former forms a type 1 Transmembrane protein, transmemb ...

, its co-receptors and IL-4R, also play important role in the regulation of SLAMF1 expression. The expression of SLAMF1 is not restricted to

immune cells White blood cells (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...

and their progenitors. From non-immune cells,

platelets Platelets or thrombocytes () are a part of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping to form a blood clot. Platelets have no cell nucleus; they are fragments of cyto ...

express SLAMF1.

Structure

SLAMF1 is a type I

transmembrane protein A transmembrane protein is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequently un ...

belonging to the

immunoglobulin superfamily The immunoglobulin superfamily (IgSF) is a large protein superfamily of cell surface and soluble proteins that are involved in the recognition, binding, or adhesion processes of cells. Molecules are categorized as members of this superfamily ...

. Its molecular weight is between 70 kDa and 95 kDa. The extracellular region of the

is composed of one Ig variable-like

domain A domain is a geographic area controlled by a single person or organization. Domain may also refer to: Law and human geography * Demesne, in English common law and other Medieval European contexts, lands directly managed by their holder rather ...

and one Ig constant 2-like

. The intracellular region of the

contains two intracellular tyrosine-based switch motives (ITSMs) that interact with

SH2 domain The SH2 (Src Homology 2) domain is a structurally conserved protein domain contained within the Src oncoprotein and in many other intracellular signal-transducing proteins. SH2 domains bind to phosphorylated tyrosine residues on other proteins, ...

-containing

proteins Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, re ...

. However, nCD150 intracellular region differs from other

of this

, it lacks ITSMs. sCD150 isoform lacks the

transmembrane domain A transmembrane domain (TMD, TM domain) is a membrane-spanning protein domain. TMDs may consist of one or several alpha-helices or a transmembrane beta barrel. Because the interior of the lipid bilayer is hydrophobic, the amino acid residues in ...

and therefore, it can not be anchored to the

cell membrane The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...

Signaling

The

SLAMF1 mediates homophilic interactions as most of the

from the SLAMF.

Signaling A signal is both the process and the result of transmission of data over some media accomplished by embedding some variation. Signals are important in multiple subject fields including signal processing, information theory and biology. ...

from SLAMF1

can be activating or inhibitory. The type of the signal depends on the

cell type A cell type is a classification used to identify cells that share morphological or phenotypical features. A multicellular organism may contain cells of a number of widely differing and specialized cell types, such as muscle cells and skin cell ...

, differentiation stage, and the combination of signals from other

-containing

, specifically adaptor proteins

SAP Sap is a fluid transported in the xylem cells (vessel elements or tracheids) or phloem sieve tube elements of a plant. These cells transport water and nutrients throughout the plant. Sap is distinct from latex, resin, or cell sap; it is a s ...

and EAT-2, and

phosphatases In biochemistry, a phosphatase is an enzyme that uses water to cleave a phosphoric acid monoester into a phosphate ion and an alcohol. Because a phosphatase enzyme catalyzes the hydrolysis of its substrate, it is a subcategory of hydrolases. Pho ...

SHP-1 Tyrosine-protein phosphatase non-receptor type 6, also known as Src homology region 2 domain-containing phosphatase-1 (SHP-1), is an enzyme that in humans is encoded by the ''PTPN6'' gene. Function The protein encoded by this gene is a member ...

SHP-2 Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) also known as protein-tyrosine phosphatase 1D (PTP-1D), Src homology region 2 domain-containing phosphatase-2 (SHP-2), or protein-tyrosine phosphatase 2C (PTP-2C) is an enzyme that in hu ...

and

SHIP A ship is a large watercraft, vessel that travels the world's oceans and other Waterway, navigable waterways, carrying cargo or passengers, or in support of specialized missions, such as defense, research and fishing. Ships are generally disti ...

, interact with ITSMs in the intracellular region of SLAMF1. Binding of

to ITSMs leads to the activation of the

kinase In biochemistry, a kinase () is an enzyme that catalyzes the transfer of phosphate groups from high-energy, phosphate-donating molecules to specific substrates. This process is known as phosphorylation, where the high-energy ATP molecule don ...

Fyn Proto-oncogene tyrosine-protein kinase Fyn (p59-FYN, Slk, Syn, MGC45350, Gene ID 2534) is an enzyme that in humans is encoded by the ''FYN'' gene. Fyn is a 59-kDa member of the Src family of kinases typically associated with T-cell and neurona ...

that phosphorylates tyrosines of SLAMF1 and recruits downstream

signaling A signal is both the process and the result of transmission of data over some media accomplished by embedding some variation. Signals are important in multiple subject fields including signal processing, information theory and biology. ...

. Because of the high affinity of

tyrosine -Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a conditionally essential amino acid with a polar side group. The word "tyrosine" is ...

phosphorylated ITSMs, it outcompetes the

which are the mediators of the inhibitory signal. Therefore, the expression and availability of

play a crucial role in the determination of the type of the signal.

Function

SLAMF1 is involved in the regulation of

thymocyte A thymocyte is an immune cell present in the thymus, before it undergoes transformation into a T cell. Thymocytes are produced as stem cells in the bone marrow and reach the thymus via the blood. Thymopoiesis describes the process which turns thy ...

development,

T cell T cells (also known as T lymphocytes) are an important part of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell ...

proliferation, differentiation and

function, such as the cytotoxic activity of

CD8+ T cells A cytotoxic T cell (also known as TC, cytotoxic T lymphocyte, CTL, T-killer cell, cytolytic T cell, CD8+ T-cell or killer T cell) is a T lymphocyte (a type of white blood cell) that kills cancer cells, cells that are infected by intracellular pa ...

and the production of IL-4, IL-13 and

IFNγ Interferon gamma (IFNG or IFN-γ) is a dimerized soluble cytokine that is the only member of the type II class of interferons. The existence of this interferon, which early in its history was known as immune interferon, was described by E. F. ...

. In

, it regulates the proliferation and the

antibody An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as pathogenic bacteria, bacteria and viruses, includin ...

production. SLAMF1 acts as a self-ligand during the interaction between

and

and promotes

lymphocyte A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include T cells (for cell-mediated and cytotoxic adaptive immunity), B cells (for humoral, antibody-driven adaptive immunity), an ...

activation. The development of NKT cells is dependent on a signal mediated by

. It was found out that the homophilic interaction of SLAMF1 or SLAMF6 is required for

recruitment in NKT cells. This interaction mediates a secondary signal crucial for NKT cell differentiation and expansion in the

thymus The thymus (: thymuses or thymi) is a specialized primary lymphoid organ of the immune system. Within the thymus, T cells mature. T cells are critical to the adaptive immune system, where the body adapts to specific foreign invaders. The thymus ...

. SLAMF1 expression in

is associated with killing of

Gram-negative bacteria Gram-negative bacteria are bacteria that, unlike gram-positive bacteria, do not retain the Crystal violet, crystal violet stain used in the Gram staining method of bacterial differentiation. Their defining characteristic is that their cell envelo ...

. SLAMF1 acts as a bacterial sensor. It is internalized after the recognition of

, and it plays a role in the regulation of

phagosome In cell biology, a phagosome is a vesicle formed around a particle engulfed by a phagocyte via phagocytosis. Professional phagocytes include macrophages, neutrophils, and dendritic cells (DCs). A phagosome is formed by the fusion of the cel ...

maturation,

ROS Ros or ROS or RoS may refer to: Organizations * Raggruppamento Operativo Speciale, the Anti-organized Crime Branch of the Italian Carabinieri * Registers of Scotland, a Scottish authority responsible for compiling and maintaining records * Repart ...

and NO production. The absence of SLAMF1 in

phagocytes Phagocytes are cell (biology), cells that protect the body by ingesting harmful foreign particles, bacteria, and dead or Apoptosis, dying cells. Their name comes from the Greek language, Greek ', "to eat" or "devour", and "-cyte", the suffix in ...

leads, among other things, to the disruption of

cytokine Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...

production.

Role of SLAMF1 in diseases

Viral infections

SLAMF1 is a

for ''Morbilliviruses.'' This

genus Genus (; : genera ) is a taxonomic rank above species and below family (taxonomy), family as used in the biological classification of extant taxon, living and fossil organisms as well as Virus classification#ICTV classification, viruses. In bino ...

viruses A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Viruses are found in almo ...

includes agents causing

measles Measles (probably from Middle Dutch or Middle High German ''masel(e)'', meaning "blemish, blood blister") is a highly contagious, Vaccine-preventable diseases, vaccine-preventable infectious disease caused by Measles morbillivirus, measles v ...

in humans,

rinderpest Rinderpest (also cattle plague or steppe murrain) was an infectious viral disease of cattle, domestic water buffalo, and many other species of even-toed ungulates, including gaurs, African Buffalo, buffaloes, large antelope, deer, giraffes, wilde ...

in cattle and distemper in dogs and cats. Ig variable-like

of SLAMF1 binds to

hemagglutinin The term hemagglutinin (alternatively spelt ''haemagglutinin'', from the Greek , 'blood' + Latin , 'glue') refers to any protein that can cause red blood cells (erythrocytes) to clump together (" agglutinate") ''in vitro''. They do this by bindin ...

on the surface of the

virus A virus is a submicroscopic infectious agent that replicates only inside the living Cell (biology), cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Viruses are ...

and this interaction mediates the

entry into the host

cell Cell most often refers to: * Cell (biology), the functional basic unit of life * Cellphone, a phone connected to a cellular network * Clandestine cell, a penetration-resistant form of a secret or outlawed organization * Electrochemical cell, a de ...

Cancer

SLAMF1 is expressed in

cancer cells Cancer cells are cells that divide continually, forming solid tumors or flooding the blood or lymph with abnormal cells. Cell division is a normal process used by the body for growth and repair. A parent cell divides to form two daughter cells, an ...

in some types of

hematologic malignancies Tumors of the hematopoietic and lymphoid tissues (American English) or tumours of the haematopoietic and lymphoid tissues (British English) are tumors that affect the blood, bone marrow, lymph, and lymphatic system. Because these tissues are all ...

(

cutaneous T-cell lymphoma Cutaneous T-cell lymphoma (CTCL) is a class of non-Hodgkin lymphoma, which is a type of cancer of the immune system. Unlike most non-Hodgkin lymphomas (which are generally B cell, B-cell-related), CTCL is caused by a mutation of T cells. The ma ...

, few types of B-cell non-Hodgkin´s lymphoma, Hodgkin´s lymphoma and about 50 % of

chronic lymphocytic leukemia Chronic lymphocytic leukemia (CLL) is a type of cancer that affects the blood and bone marrow. In CLL, the bone marrow makes too many lymphocytes, which are a type of white blood cell. In patients with CLL, B cell lymphocytes can begin to colle ...

cases). It regulates

cancer cell Cancer cells are cells that divide continually, forming solid tumors or flooding the blood or lymph with abnormal cells. Cell division is a normal process used by the body for growth and repair. A parent cell divides to form two daughter cells, an ...

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. Several cases of

leukemia Leukemia ( also spelled leukaemia; pronounced ) is a group of blood cancers that usually begin in the bone marrow and produce high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or '' ...

or Hodgkin´s lymphoma remission after

measles virus The measles virus (MV), with scientific name ''Morbillivirus hominis'', 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. H ...

infection or

vaccination Vaccination is the administration of a vaccine to help the immune system develop immunity from a disease. Vaccines contain a microorganism or virus in a weakened, live or killed state, or proteins or toxins from the organism. In stimulating ...

have been described. Therefore, SLAMF1 could be used as a target for cancer therapy which is based on the

-mediated

lysis Lysis ( ; from Greek 'loosening') is the breaking down of the membrane of a cell, often by viral, enzymic, or osmotic (that is, "lytic" ) mechanisms that compromise its integrity. A fluid containing the contents of lysed cells is called a ...

of the

. nCD150 isoform was found in tumors of the central nervous system, such as

glioblastoma Glioblastoma, previously known as glioblastoma multiforme (GBM), is the most aggressive and most common type of cancer that originates in the brain, and has a very poor prognosis for survival. Initial signs and symptoms of glioblastoma are nons ...

, anaplastic and diffuse

astrocytoma Astrocytoma is a type of brain tumor. Astrocytomas (also astrocytomata) originate from a specific kind of star-shaped glial cell in the cerebrum called an astrocyte. This type of tumor does not usually spread outside the brain and spinal cord, an ...

and

ependymoma An ependymoma is a tumor that arises from the ependyma, a tissue of the central nervous system. Usually, in pediatric cases the location is intracranial, while in adults it is spinal. The common location of intracranial ependymomas is the floor ...

References

External links

* {{Clusters of differentiation Clusters of differentiation