Selectin P ligand, also known as SELPLG or CD162 (
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 immunophen ...
162), is a human
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.
SELPLG codes for PSGL-1, the high affinity counter-receptor for P-selectin on myeloid cells and stimulated T lymphocytes. As such, it plays a critical role in the tethering of these cells to activated platelets or endothelia expressing P-selectin.
The organization of the SELPLG gene closely resembles that of
CD43
Leukosialin also known as sialophorin or CD43 (cluster of differentiation 43) is a transmembrane cell surface protein that in humans is encoded by the ''SPN'' (sialophorin) gene.
Function
Sialophorin (leukosialin) is a major sialoglycoprotein ...
and the human platelet glycoprotein
GpIb-alpha both of which have an intron in the 5-prime-noncoding region, a long second exon containing the complete coding region, and TATA-less promoters.
P-selectin glycoprotein ligand-1 (PSGL-1) is a
glycoprotein found on
white blood cells
White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...
and
endothelial
The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel ...
cells that binds to
P-selectin
P-selectin is a type-1 transmembrane protein that in humans is encoded by the SELP gene.
P-selectin functions as a cell adhesion molecule (CAM) on the surfaces of activated endothelial cells, which line the inner surface of blood vessels, and act ...
(P stands for
platelet
Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby i ...
), which is one of a family of selectins that includes
E-selectin
E-selectin, also known as CD62 antigen-like family member E (CD62E), endothelial-leukocyte adhesion molecule 1 (ELAM-1), or leukocyte-endothelial cell adhesion molecule 2 (LECAM2), is a selectin cell adhesion molecule expressed only on endothelial ...
(endothelial) and
L-selectin
L-selectin, also known as CD62L, is a cell adhesion molecule found on the cell surface of leukocytes, and the blastocyst. It is coded for in the human by the ''SELL'' gene. L-selectin belongs to the selectin family of proteins, which recognize si ...
(leukocyte). Selectins are part of the broader family of
cell adhesion molecule
Cell adhesion molecules (CAMs) are a subset of cell surface proteins that are involved in the binding of cells with other cells or with the extracellular matrix (ECM), in a process called cell adhesion. In essence, CAMs help cells stick to each ...
s. PSGL-1 can bind to all three members of the family but binds best (with the highest affinity) to P-selectin.
Posttranslational modification
PSGL-1 protein requires two distinct
posttranslational modification
Post-translational modification (PTM) is the covalent and generally enzymatic modification of proteins following protein biosynthesis. This process occurs in the endoplasmic reticulum and the golgi apparatus. Proteins are synthesized by ribo ...
s to gain its selectin binding activity:
*
sulfation
Sulfation is the chemical reaction that entails the addition of SO3 group. In principle, many sulfations would involve reactions of sulfur trioxide (SO3). In practice, most sulfations are effected less directly. Regardless of the mechanism, the ...
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 non-essential amino acid with a polar side group. The word "tyrosine" is from the G ...
s
* the addition of the
sialyl Lewis x
Sialyl LewisX (sLeX), also known as cluster of differentiation 15s (CD15s) or stage-specific embryonic antigen 1 (SSEA-1), is a tetrasaccharide carbohydrate which is usually attached to O- glycans on the surface of cells. It is known to play a vi ...
tetrasaccharide (sLex) to its O-linked
glycans
Function
PSGL-1 is expressed on all
white blood cells
White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...
and plays an important role in the recruitment of white blood cells into inflamed tissue: White blood cells normally do not interact with the
endothelium
The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vesse ...
of blood vessels. However,
inflammation
Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molec ...
causes the expression of cell adhesion molecules (CAM) such as P-selectin on the surface of the blood vessel wall. White blood cells present in flowing blood can interact with CAM. The first step in this interaction process is carried out by PSGL-1 interacting with P-selectin and/or E-selectin on endothelial cells and adherent platelets. This interaction results in "rolling" of the white blood cell on the endothelial cell surface followed by stable adhesion and transmigration of the white blood cell into the inflamed tissue.
In mice it seems to be an immune factor regulating
T-cell checkpoints
Immune checkpoints are regulators of the immune system. These pathways are crucial for self-tolerance, which prevents the immune system from attacking cells indiscriminately. However, some cancers can protect themselves from attack by stimula ...
, and it could be a target for future
checkpoint inhibitor
Checkpoint inhibitor therapy is a form of cancer immunotherapy. The therapy targets immune checkpoints, key regulators of the immune system that when stimulated can dampen the immune response to an immunologic stimulus. Some cancers can protect the ...
anti-cancer drugs.
PSGL-1 has been shown to bind to VISTA (V-domain Ig suppressor of T cell activation) but this binding only occurs under acidic pH conditions (pH < 6.5) such as can be found in tumor microenvironments (TME).
[ Nature. 2019 Oct;574(7779):565-570. doi: 10.1038/s41586-019-1674-5. Epub 2019 Oct 23. PMID: 31645726 ][
]
References
Further reading
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External links
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{{Clusters of differentiation
Clusters of differentiation
Receptors