Transcriptional Regulation of Cystathionine-gamma-Lyase in Endothelial Cells by NADPH Oxidase 4-Dependent Signaling.
Authors: Mistry R, Murray T, Prysyazhna O, Martin D, Burgoyne J, Santos C, Eaton P, Shah A, Brewer A
J Biol Chem, 2016;291(4):1774-88.
Species: Mouse
Sample Type: Tissue Homogenates
Application: Clustering
Filter-Dense Multicolor Microscopy.
Authors: Kijani S, Yrlid U, Heyden M, Levin M, Boren J, Fogelstrand P
PLoS ONE, 2015;10(3):e0119499.
Species: Mouse
Sample Type: Whole Tissue
Application: IHC - Not specified

PECAM-1 (platelet-endothelial cell adhesion molecule-1; also known as CD31) is a 130 kDa type I transmembrane glycoprotein adhesion molecule in the immunoglobulin superfamily (1, 2). Expression is restricted to cells involved in circulation, especially endothelial cells, platelets, monocytes, neutrophils and lymphocyte subsets. PECAM-1 is concentrated at cell-cell junctions and is required for transendothelial migration (TEM) (1-3). The extracellular domain (ECD) of PECAM-1 has ten potential N-linked glycosylation sites and six C2-type Ig-like domains, the first of which is critical for adhesion and extravasation (3, 4). The cytoplasmic domain contains immunoregulatory tyrosine-based inhibitory and switch motifs (ITIM, ITSM) that mediate both inhibition and activation via phosphotyrosine-mediated engagement of SH2-containing signaling molecules (1, 5). Metalloproteinase-mediated ectodomain shedding occurs during apoptosis (6) but increased serum PECAM-1 ectodomain in HIV and active multiple sclerosis occurs independent of apoptosis (7, 8). In humans, expression of six isoforms with exon deletions in the cytoplasmic domain is tissue- and stage-specific, but full-length PECAM-1 is predominant. A form lacking the ITSM predominates in mouse (9). Mouse PECAM-1 ECD shows 77%, 63%, 63%, 63%, and 61% amino acid (aa) identity with rat, human, canine, porcine, and bovine PECAM-1, respectively. PECAM-1 participates with other adhesion molecules in some functions, but is the critical molecule for TEM. Homotypic PECAM-1 adhesion in trans, combined with cycling of PECAM-1 to and from surface-connected endothelial cell vesicles, leads leukocytes across endothelial tight junctions (3, 10). Homotypic adhesion and signaling functions also strongly suppress mitochondria-dependent apoptosis (11). In platelets, PECAM-1 is necessary for limiting thrombus formation (12) and promoting integrin-mediated clot retraction and platelet spreading (13), but mechanisms for these phenomena are unclear. PECAM^-/- mice are deficient in chemokine-mediated chemotaxis (14).

1. Ilan, N. and J.A. Madri (2003) Curr. Opin. Cell Biol. 15:515.
2. Xie, Y. and W.A. Muller (1993) Proc. Natl. Acad. Sci. USA 90:5569.
3. Liao, F. et al. (1997) J. Exp. Med. 185:1349.
4. Nakada, M.T. et al. (2000) J. Immunol. 164:452.
5. Chemnitz, J.M. et al. (2004) J. Immunol. 173:945.
6. Ilan, N. et al. (2001) FASEB J. 15:362.
7. Eugenin, E.A. et al. (2006) J. Leukoc. Biol. 79:444.
8. Losy, J. et al. (1999) J. Neuroimmunol. 99:169.
9. Wang, Y. et al. (2003) Am. J. Physiol. Heart Circ. Physiol. 284:H1008.
10. Mamdouh, Z. et al. (2003) Nature 421:748.
11. Gao, C. et al. (2003) Blood 102:169.
12. Falati, S. et al. (2006) Blood 107:535.
13. Wee, J.L. and D.E. Jackson (2005) Blood 106:3816.
14. Wu, Y. et al. (2005) J. Immunol. 175:3484.