|CD162||SELPLG (selectin P ligand), PSGL-1 (P-selectin glycoprotein ligand 1)|
|Molecule Type||Antigen Expression||Molecular Weight|
Min / Max
|Non-lineage Restricted Molecule|
Type 1 glycoprotein
|120 / 120|
160 / 160
250 / 250
|CD162 is expressed on most peripheral blood T cells, monocytes, stem cells, granulocytes, and most lymphocytes. On neutrophils CD162 is concentrated on the tips of microvilli. Some B cells express CD162. Some CD34+ positive bone marrow cells express CD162. In the mouse, CD162 mRNA has been detected in most tissues.|
|MOLECULAR FAMILY NAME: Belongs to the mucin family.|
CD162 is a disulfide-linked homodimeric mucin-like single-pass type-1 361 aa
glycoprotein. It contains a 303 aa extracellular domain which contains 16 10aa repeats, 3 potential glycosylation sites and a complex of sialylated and fucosylated O-linked oligosaccharides some of which appear to contain poly-N-acetyllactosamine, a 25 aa transmembrane domain, and a 69 aa intracellular cytoplasmic domain. Most cell lines have CD162 molecules with 15 repeats, whereas CD162 present in most leukocytes have 16 repeats. The interaction of the cytoplasmic domain with the leukocyte cortical cytoskeleton is aqn essential requirement for leukocyte rolling on CD62P. The organization of the SELPLG gene closely resembles that of CD43 and the human platelet glycoprotein GpIb-α 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.
The protein-coding sequence is in a single exon, so alternative splicing should not be possible.
CD162 has 3 possible N-linked glycosylation sites and many potential O-linked glycosylation sites are present in the extracellular region which is critical for recognition and binding to CD62P and CD62E. Most of the N-glycan sites and many of the O-glycan sites are occupied. The structures of the O-glycans of PSGL-1 from human HL60 cells have been determined. A subset of the O-glycans is core-2, sialylated and fucosylated structures, which are required for binding to selectins. Tyrosine sulfation of the amino-terminal region of PSGL-1 is required for binding to P-selectin and L-selectin. There is an N-terminal pro-peptide that is probably cleaved post-translationally. The N-terminal region is sulfated which is necessary for P-selectin binding.
|CD162 binds to CD62P-selectin, CD62E-selectin, and CD62L-selectin. CD62P binds with a relatively high affinity, apparently utilizing both carbohydrate fucosylated and sialylated O-glycans and protein determinants with the latter including sulfotyrosine-containing N-terminal region. CD62L binding also requires this sulfotyrosine-containing region. In contrast, CD62E binds with a ~50-fold lower avidity than CD62P and does not require the sulfotyrosine-containing region. CD62P does not bind all cells which express CD162, presumably because of differences in glycosylation and/or tyrosine sulfation. For example, CD62P will bind activated but not resting T cells, despite no change in the CD162 expression level.|
LIGANDS AND MOLECULES ASSOCIATED WITH CD162
Post-translational modifications of PSGL-1 are critical for recognition. Core-2, sialylated and fucosylated O-glycans are required for PSGL-1 to bind all 3 selectins. Tyrosine sulfation is also required for PSGL-1 to bind P- and L-selectin.
|CD162 binds to P-, E- and L-selectins (CD62P, CD62E and CD62L). CD162 is the high affinity counter-receptor for P-selectin on myeloid cells, neutrophils and T lymphocytes. The calcium-dependent high affinity interaction with P-selectin mediates adhesion, rolling and tethering of leukocytes on endothelial cells, activated platelets and other leukocytes at sites of inflammation. Cross-linking of CD162 with certain mAb has been shown to induce caspase-independent death of activated T cells but not resting T cells and did not interfer with binding to P-selectin. It plays a critical role in the tethering of these cells to activated platelets or endothelia expressing P-selectin. It also reacts to activated endothelium and on other leukocytes at inflammatory sites. Interactions between CD162 and CD62L can mediate neutrophil-neutrophil interactions, which may amplify neutrophil extravasation. |
BIOCHEMICAL ACTIVITY: No information.
DISEASE RELEVANCE AND FUNCTION OF CD162 IN INTACT ANIMAL
CD162 uses antibodies in murine models of GVHD and type 1 diabetes mellitus ameliorated the diseases. There is a function for CD162 in the trafficking of a specific subset of T cells in a mouse model. CD162 knockout mice have impaired rolling and migration of leukocytes.
CD162 mediates rolling of human neutrophils that are perfused into rat mesenteric venules. CD162 may be a useful marker for differentiating myelblasts from mononlasts in immunophenotyping of AML subsets. CD162 is currently being investigated as a therapeutic target in the treatment of autoimmune disease and in chronic T cell mediated diseases.
|MOLECULAR INTERACTIONS -|
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD162: No information.
SUBSTRATES: No information.
ENZYMES WHICH MODIFY CD162: No information.
Database accession numbers
Revised June 25, 2008