Abstract

This renewal application proposes to study in-depth the cell and molecular biology of Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1), a cell-cell adhesion molecular of the immunoglobulin gene superfamily that is expressed on endothelial cells, platelets and leukocytes, and was originally described by the Applicant. Studies of the regulation of the adhesive activity and expression of PECAM-1 are proposed. Specifically, experiments are planned to identify specific regions of the extracellular domain of PECAM- 1 that are involved in both homophilic and heterophilic PECAM-1 mediated interactions. The second series of studies will examine the role of posttranslational changes in the cytoplasmic domain of PECAM-1 (specifically phosphorylation and palmitoylation), effected by site- directed mutagenesis, in the control of the subcellular distribution and adhesive properties of the molecule. Finally, a series of experiments is proposed to characterize the regulatory domains within the recently defined PECAM-1 promoter.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL040926-12
Application #
6030582
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1988-07-01
Project End
2000-06-30
Budget Start
1999-07-01
Budget End
2000-06-30
Support Year
12
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
Bloodcenter of Wisconsin, Inc.
Department
Type
DUNS #
City
Milwaukee
State
WI
Country
United States
Zip Code
53233

  Publications

Liao, Danying; Mei, Heng; Hu, Yu et al. (2018) CRISPR-mediated deletion of the PECAM-1 cytoplasmic domain increases receptor lateral mobility and strengthens endothelial cell junctional integrity. Life Sci 193:186-193
Newman, Debra K; Fu, Guoping; McOlash, Laura et al. (2018) Frontline Science: PECAM-1 (CD31) expression in naïve and memory, but not acutely activated, CD8+ T cells. J Leukoc Biol 104:883-893
Paddock, Cathy; Zhou, Dongwen; Lertkiatmongkol, Panida et al. (2016) Structural basis for PECAM-1 homophilic binding. Blood 127:1052-61
Lertkiatmongkol, Panida; Liao, Danying; Mei, Heng et al. (2016) Endothelial functions of platelet/endothelial cell adhesion molecule-1 (CD31). Curr Opin Hematol 23:253-9
Newman, Debra K; Fu, Guoping; Adams, Tamara et al. (2016) The adhesion molecule PECAM-1 enhances the TGF-?-mediated inhibition of T cell function. Sci Signal 9:ra27
Privratsky, Jamie R; Newman, Peter J (2014) PECAM-1: regulator of endothelial junctional integrity. Cell Tissue Res 355:607-19
Mei, Heng; Campbell, Jay M; Paddock, Cathy M et al. (2014) Regulation of endothelial cell barrier function by antibody-driven affinity modulation of platelet endothelial cell adhesion molecule-1 (PECAM-1). J Biol Chem 289:20836-44
Tourdot, Benjamin E; Brenner, Michelle K; Keough, Kathleen C et al. (2013) Immunoreceptor tyrosine-based inhibitory motif (ITIM)-mediated inhibitory signaling is regulated by sequential phosphorylation mediated by distinct nonreceptor tyrosine kinases: a case study involving PECAM-1. Biochemistry 52:2597-608
Kuckleburg, Christopher J; Newman, Peter J (2013) Neutrophil proteinase 3 acts on protease-activated receptor-2 to enhance vascular endothelial cell barrier function. Arterioscler Thromb Vasc Biol 33:275-84
Privratsky, Jamie R; Tilkens, Sarah B; Newman, Debra K et al. (2012) PECAM-1 dampens cytokine levels during LPS-induced endotoxemia by regulating leukocyte trafficking. Life Sci 90:177-84

Showing the most recent 10 out of 48 publications