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Platelet-endothelial cell adhesion molecule-1 (CD31), a scaffolding molecule for selected catenin family members
1Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Insights
Platelet-endothelial cell adhesion molecule (PECAM)-1 interacts with beta-catenin and gamma-catenin, influencing their localization and phosphorylation. This reveals PECAM-1
Area of Science:
- Molecular and Cell Biology
- Immunology
- Biochemistry
Background:
- Platelet-endothelial cell adhesion molecule (PECAM)-1 is recognized as an endothelium-specific marker.
- Emerging evidence indicates PECAM-1's role extends beyond cell marking, involving signal transduction pathways.
- PECAM-1's function is modulated by phosphorylation and the recruitment of signaling molecules.
Purpose of the Study:
- To investigate the association of PECAM-1 with catenins beyond beta-catenin.
- To elucidate the role of protein kinase C (PKC) in PECAM-1 phosphorylation and catenin interaction.
- To understand the molecular mechanisms underlying PECAM-1's interaction with the cytoskeleton.
Main Methods:
- In vitro and in vivo association studies of PECAM-1 with beta-catenin and gamma-catenin.
- In vitro phosphorylation assays using purified PECAM-1 and PKC enzyme.
- Analysis of catenin association with PECAM-1 phosphorylation.
- Cellular localization studies in transfected SW480 cells.
- Investigation of PECAM-1 recruitment into cytoskeletal fractions.
Main Results:
- PECAM-1 associates with both beta-catenin and gamma-catenin.
- PKC directly phosphorylates PECAM-1, and this serine/threonine phosphorylation inversely correlates with gamma-catenin association.
- PECAM-1 facilitates gamma-catenin recruitment to cell-cell junctions, and gamma-catenin may anchor PECAM-1 to the cytoskeleton.
Conclusions:
- PECAM-1 acts as a crucial binder and modulator of catenins.
- The findings provide a molecular basis for PECAM-1's involvement in cytoskeleton interactions.
- This study expands the understanding of PECAM-1's multifaceted roles in cellular signaling and adhesion.
Abstract:
Platelet-endothelial cell adhesion molecule (PECAM)-1 is a 130-kDa glycoprotein commonly used as an endothelium-specific marker. Evidence to date suggests that PECAM-1 is more than just an endothelial cell marker but is intimately involved in signal transduction pathways. This is mediated in part by phosphorylation of specific tyrosine residues within the ITAM domain of PECAM-1 and by recruitment of adapter and signaling molecules. Recently we demonstrated that PECAM-1/beta-catenin association functions to regulate beta-catenin localization and, moreover, to modulate beta-catenin tyrosine phosphorylation levels. Here we show that: 1) not only beta-catenin, but also gamma-catenin is associated with PECAM-1 in vitro and in vivo; 2) PKC enzyme directly phosphorylates purified PECAM-1; 3) PKC-derived PECAM-1 serine/threonine phosphorylation inversely correlates with gamma-catenin association; 4) PECAM-1 recruits gamma-catenin to cell-cell junctions in transfected SW480 cells; and 5) gamma-catenin may recruit PECAM-1 into an insoluble cytoskeletal fraction. These data further support the concept that PECAM-1 functions as a binder and modulator of catenins and provides a molecular mechanism for previously reported PECAM-1/cytoskeleton interactions.