Role of lateral cell-cell border location and extracellular/transmembrane domains in PECAM/CD31 mechanosensation.
Phosphorylation of tyrosine residues on platelet-endothelial cell adhesion molecule-1 (PECAM-1), followed by signal transduction events, has been described in endothelial cells following exposure to hyperosmotic and fluid shear stress. However, it is unclear whether PECAM-1 functions as a primary mechanosensor in this process. Utilizing a PECAM-1-null EC-like cell line, we examined the importance of cellular localization and the extracellular and transmembrane domains in PECAM-1 phosphorylation responses to mechanical stress. Tyrosine phosphorylation of PECAM-1 was stimulated in response to mechanical stress in null cells transfected either with full length PECAM-1 or with PECAM-1 mutants that do not localize to the lateral cell-cell adhesion site and that do not support homophilic binding between PECAM-1 molecules. Furthermore, null cells transfected with a construct that contains the intact cytoplasmic domain of PECAM-1 fused to the extracellular and transmembrane domains of the interleukin-2 receptor also underwent mechanical stress-induced PECAM-1 tyrosine phosphorylation. These findings suggest that mechanosensitive PECAM-1 may lie downstream of a primary mechanosensor that activates a tyrosine kinase.
Kaufman
David A
DA
Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, USA.
Albelda
Steven M
SM
Sun
Jing
J
Davies
Peter F
PF
D002448:Cell Adhesion / Q000502:physiology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans; D040542:Mechanotransduction, Cellular; D008654:Mesothelioma / Q000378:metabolism* / Q000473:pathology*; D016297:Mutagenesis, Site-Directed; D009997:Osmotic Pressure; D010766:Phosphorylation; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism*; D013314:Stress, Mechanical; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
D019408:Platelet Endothelial Cell Adhesion Molecule-1