Phosphorylation of leukocyte PECAM and its association with detergent-resistant membranes regulate transendothelial migration Journal Article
| Authors: | Florey, O.; Durgan, J.; Muller, W. |
| Article Title: | Phosphorylation of leukocyte PECAM and its association with detergent-resistant membranes regulate transendothelial migration |
| Abstract: | Leukocyte migration across the endothelial lining is a critical step in the body's response to infection and inflammation. The homophilic interaction between endothelial PECAM and leukocyte PECAM is essential for this process. The molecular events that are triggered in the endothelial cell by PECAM engagement have been well characterized; however, the function of leukocyte PECAM remains to be elucidated. To study this, we first blocked leukocyte transmigration using anti-PECAM Ab and then specifically activated leukocyte PECAM. This was sufficient to overcome the block and promote transmigration, suggesting an active signaling role for leukocyte PECAM. Consistent with this, we found that ligation of leukocyte PECAM induces phosphorylation of two tyrosine residues on its cytoplasmic tail. By performing RNA interference-rescue experiments, we demonstrate that these phosphorylation events are indispensable for transendothelial migration. Finally, we show that leukocyte PECAM translocates to a detergent-resistant membrane (DRM) during transmigration. PECAM localized in DRMs displays reduced phosphorylation and does not support transmigration. Together, these data support a model whereby engagement of leukocyte PECAM induces its transient tyrosine phosphorylation and induction of downstream signals that drive transmigration. These signals are then downregulated following PECAM translocation to DRMs. Copyright © 2010 by The American Association of Immunologists, Inc. |
| Keywords: | signal transduction; controlled study; protein phosphorylation; unclassified drug; human cell; protein localization; cytology; metabolism; cell line; down-regulation; cell motion; rna interference; tyrosine; phosphorylation; physiology; endothelium cell; immunology; chemistry; vascular endothelium; endothelium, vascular; cell membrane; protein transport; cell migration; cell movement; down regulation; monocyte; monocytes; cell activation; antibody; leukocyte; cd31 antigen; membrane lipid; cell adhesion molecule; cell strain u937; u937 cells; detergent; platelet endothelial cell adhesion molecule; beta cyclodextrin derivative; blocking antibody; cross linking reagent; methyl beta cyclodextrin; methyl-beta-cyclodextrin; neutralizing antibody; octoxinol; cross linking; antibodies, blocking; antibodies, neutralizing; antigens, cd31; beta-cyclodextrins; cross-linking reagents; detergents; membrane lipids; octoxynol |
| Journal Title: | Journal of Immunology |
| Volume: | 185 |
| Issue: | 3 |
| ISSN: | 0022-1767 |
| Publisher: | The American Association of Immunologists, Inc |
| Date Published: | 2010-08-01 |
| Start Page: | 1878 |
| End Page: | 1886 |
| Language: | English |
| DOI: | 10.4049/jimmunol.1001305 |
| PUBMED: | 20581150 |
| PROVIDER: | scopus |
| PMCID: | PMC3099243 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 20 April 2011" - "CODEN: JOIMA" - "Source: Scopus" |
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