• P-selectin
• granule membrane protein-140, GMP-140
• platelet activation dependent granule-external membrane protein, PADGEM

MAJOR LINKS FOR CD62P  

• NCBI LocusLink Record: 6403
• Mendelian Inheritance in Man (OMIM): 173610
• SwissProt annotated protein record: P16109

CELLULAR FUNCTION OF CD62P  

• Interaction of CD62P with PSGL-1 mediates tethering and rolling of leukocytes on the surface of activated endothelial cells, the first step in leukocyte extravasation and migration towards inflammations
• CD62P mediates rolling of platelets on endothelial cells; CD62P-mediated interactions are also involved in platelet-mediated delivery of lymphocytes to high endothelial venules

DISEASE RELEVANCE OF CD62P AND FUNCTION OF CD62P IN INTACT ANIMAL  

• 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
• CD62P knockout mice display reduced rolling of leukocytes on endothelia (intravital microscopy) and decreased neutrophil, monocyte and CD4+T cell recruitment into inflamed tissues*
• In contrast to single knockouts, CD62P and CD62E double knockouts present with extreme leukocytosis, altered hematopoiesis and increased susceptibility to infection

• Families in which CD62P is a member
  • CD62P-->selectin-->c-type lectin

MOLECULAR STRUCTURE OF CD62P  

• Long single chain type I transmembrane molecule of 789 amino acids
• 730 amino acids in the extracellular domain
• Extracellular part consists of an N-terminal lectin domain, followed by an EGF domain and 9 consensus repeats homologous to domains found in complement-binding proteins
• 24 amino acids in the transmembrane domain
• 35 amino acids in the cytoplasmic domain

MOLECULAR MASS OF CD62P  

POST-TRANSCRIPTIONAL MODIFICATION OF CD62P  

• A soluble form of CD62P lacking the transmembrane domain as a result of alternative splicing has been identified in blood plasma

POST-TRANSLATIONAL MODIFICATION OF CD62P  

• Extensive N-linked glycosylation (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

SUBSTRATES FOR CD62P   - No information

ENZYMES WHICH MODIFY CD62P   - No information

LIGANDS FOR CD62P AND MOLECULES ASSOCIATED WITH CD62P  

• 160-kDa ligand found on mouse myeloid cells

• CD62P is mobilized from storage granules to the cell surface after activation of the cells
• CD62P is also rapidly internalized from endothelial cell surface

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

SELECTION OF OTHER CD62P-SPECIFIC REFERENCE MAB  

REVIEWS

1. McEver RP,Moore KL,Cummings RD Leukocyte trafficking mediated by selectin-carbohydrate interactions. J Biol Chem 1995 270:11025 PubMed

2. Varki A Selectin ligands. Proc Natl Acad Sci U S A 1994 91:7390 PubMed

PRIMARY CITATIONS

3. Crovello CS,Furie BC,Furie B Histidine phosphorylation of P-selectin upon stimulation of human platelets: a novel pathway for activation-dependent signal transduction. Cell 1995 82:279 PubMed

4. Diacovo TG,Puri KD,Warnock RA,Springer TA,von Andrian UH Platelet-mediated lymphocyte delivery to high endothelial venules. Science 1996 273:252 PubMed

5. Frenette PS,Johnson RC,Hynes RO,Wagner DD Platelets roll on stimulated endothelium in vivo: an interaction mediated by endothelial P-selectin. Proc Natl Acad Sci U S A 1995 92:7450 ** PubMed

6. Frenette PS,Mayadas TN,Rayburn H,Hynes RO,Wagner DD Susceptibility to infection and altered hematopoiesis in mice deficient in both P- and E-selectins. Cell 1996 84:563 PubMed

7. Fujimoto T,Stroud E,Whatley RE,Prescott SM,Muszbek L,Laposata M,McEver RP P-selectin is acylated with palmitic acid and stearic acid at cysteine 766 through a thioester linkage. J Biol Chem 1993 268:11394 PubMed

8. Johnston GI,Cook RG,McEver RP Cloning of GMP-140, a granule membrane protein of platelets and endothelium: sequence similarity to proteins involved in cell adhesion and inflammation. Cell 1989 56:1033 PubMed

9. Mayadas TN,Johnson RC,Rayburn H,Hynes RO,Wagner DD Leukocyte rolling and extravasation are severely compromised in P selectin-deficient mice. Cell 1993 74:541 PubMed

10. Norman KE,Moore KL,McEver RP,Ley K Leukocyte rolling in vivo is mediated by P-selectin glycoprotein ligand- Blood 1995 86:4417 PubMed

11. Pan J,McEver RP Regulation of the human P-selectin promoter by Bcl-3 and specific homodimeric members of the NF-kappa B/Rel family. J Biol Chem 1995 270:23077 PubMed

12. Sako D,Chang XJ,Barone KM,Vachino G,White HM,Shaw G,Veldman GM,Bean KM,Ahern TJ,Furie B,et al Expression cloning of a functional glycoprotein ligand for P-selectin. Cell 1993 75:1179 PubMed

WWW RESOURCES

Portions copyright by Garland Press and by the International Workshops on Human Leukocyte Differentiation Antigens; used with permission

Modified 10/14/99   mpr@mail.nih.gov