CD62P P-Selection,  GMP-140 (granule membrane protein), PADGEM (platelet activation dependent granule external membrane protein), SELP (selectin P)
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
Platelet
Endothelial Cell
Megakaryocyte
Endothelium
Plasma
Lysosome
120 / 120
140 / 140

Expression
CD62P is present on megakaryocytes, activated platelets and endothelium.  It is stored in secretory granules in platelets and endothelial cells and is rapidly translocated to the plasma membrane upon activation of these cells.  Expression is transient as CD62P is rapidly internalized and then degraded in lysosomes.  Soluble forms of CD62P originating from alternative splicing and possible proteolytic cleavage are detectable in plasma at levels of 0.1-1 mg/ml.


Structure
MOLECULAR FAMILY NAME:   Belongs to the selectin C-type lectin family.

CD62P is a long single-pass type-1 789 aa glycoprotein.  It contains a 730 aa extracellular domain which contains a N-terminal C-type domain, an epidermal growth factor (EGF ) domain and 9 complement control binding protein (CCP) domains, a 24 aa transmembrane domain and a 35 aa cytoplasmic domain.  It is a member of the selectin family of cellular adhesion molecules which includes CD62E E-selectin and CD62L L-selectin.  The extracellular portion forms an extended rod approximately 48 nm long.  The short cytoplasmic domain, which bears no homology to the CD62E or CD62L cytoplasmic domains, is phosphorylated on Ser, Thr, Tyr and His residues following platelet activation.

MOLECULAR MASS
Cell Type Unreduced Reduced
Platelets 120 kDa 140 kDa
Endothelial cells 120 kDa 140 kDa

POST-TRANSCRIPTIONAL MODIFICATION

A soluble form of CD62P lacking the transmembrane domain as a result of alternative splicing, gives rise to molecules that lack exon 11 (encoding the 7th CCP domain) or lacking exon 14 have been identified in blood plasma.   

POST-TRANSLATIONAL MODIFICATION

There is extensive N-linked glycosylation of 29% of MW. Activation of platelets induces rapid but transient phosphorylation of CD62P Ser, Thr, Tyr and His residues.  Cytoplasmic Cys 766 is acylated with palmitic and stearic acid.

Ligands
Like CD62E and CD62L, CD62P binds a low affinity to anionic oligosaccharide sequences related to sialylated Lewis x (sLe x, CD15s) through its C-type lectin domain.  CD62P and CD62L also bind various structurally unrelated anionic carbohydrates such as heparin sulfate (HS) and sulfatides.  The major CD62P ligand on neutrophils is the mucin-like cell surface glycoprotein CD162 PSGL-1.  Optimal binding to CD162 requires O-linked sLe x-like structures as well as sulfated NH2-terminal tyrosines.  The conserved EGF domain of P-selectin is required for optimal binding, and it has been suggested that it may contain a 2nd binding site which interacts with the sulfotyrosine-containing region for CD162.  Mouse CD62P has been reported to bind certain glycoforms of the mucin CD24.

LIGANDS AND MOLECULES ASSOCIATED WITH CD62P
Molecule Comment
CD162 (PSGL-1) (P-selectin glycoprotein ligand-1) A 240 kDa homodimeric (disulfide-linked) ligand for CD62P present on most myeloid cells, as well as on subsets of lymphocytes. Other lymphocytes contain nonfunctional forms of PSGL-1
CD24 Found on human myeloid and tumor cells


A ligand of 160-kDa is found on mouse myeloid cells.



Function
Endothelial CD62P mediates the rolling of neutrophils on activated endothelium, a prerequisite for recruitment of neutrophils into areas of inflammation.  CD62P appears to be particularly important within minutes with other selectins contributing at later stages.  Endothelial CD62P also mediates rolling of platelets and some T lymphocyte subsets.  CD62P on adherent platelets promotes leukocyte accumulation in thrombi. Platelet CD62P can also contribute indirectly to T lymphocyte homing to high endothelial venules (HEVs). Activated CD62P+ platelets attached to lymphocytes can mediate lymphocyte rolling through an interaction between platelet CD62P and endothelial peripheral node addressin.  Mice deficient in CD62P show reduced neutrophil rolling and delayed recruitment into inflamed tissues. CD62P and CD62E have overlapping roles since mice deficient in both CD62P and CD62E show many defects in leukocyte extravasation and are susceptible to opportunistic infections.

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD62P IN INTACT ANIMAL

CD62P is implicated in the metastasis of various carcinomas as CD24-expressing tumor cells bind P-selectin on platelets and form thrombi, which protects tumor cells from immune destruction while circulating.  This binding of CD62P to CD24 enables rolling of tumor cells on vascular endothelium in the process of extravasation and tissue penetration during metastasis.  CD62P expression during inflammation can result in thrombosis, atherogenesis and tissue destruction.  CD62P mediates interactions of leukocytes with the blood vessel wall.  CD62P monoclonal antibody inhibition studies in animal models show a critical role for CD62P in leukocyte emigration in a variety of experimentally induced inflammation reactions and may be a potential target for treatment of chronic inflammatory diseases such as asthma.  CD62P knockout mice display reduced rolling of leukocytes on endothelium by intravital microscopy and decreased neutrophil, monocyte and CD4+ T cell recruitment into inflamed tissues.  In contrast to single knockouts, CD62P and CD62E double knockout mice demonstrate that the roles of CD62P and CD62E overlap, as the inflammation defects are more severe.  These mice have severe leukocytosis,altered hematopoiesis and increased susceptibility to infection.

Comments
MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD62P
Molecule Comment
NK-kB/Rel p50
p52 homodimers
IkBa-related inhibitor Bcl-3

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD62P: No information.

ADDITIONAL INSIGHTS

Constitutive CD62P expression in inflammation may contribute to tissue destruction, atherogenesis and thrombosis.

Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 6403P16109
MouseA42755Q01102M87861
RatP98106L23088
Antibodies
1E3   View Reactivity
AC1.2   View Reactivity
AK-4   View Reactivity
AK-6   View Reactivity

Revised June 25, 2008


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