Leukocyte transmigration is modulated by chemokine-mediated PI3Kgamma-dependent phosphorylation of vimentin

Barberis, Laura and Pasquali, Christian and Bertschy-Meier, Dominique and Cuccurullo, Alessandra and Costa, Carlotta and Ambrogio, Chiara and Vilbois, Francis and Chiarle, Roberto and Wymann, Matthias and Altruda, Fiorella and Rommel, Christian and Hirsch, Emilio. (2009) Leukocyte transmigration is modulated by chemokine-mediated PI3Kgamma-dependent phosphorylation of vimentin. European journal of immunology, Vol. 39. pp. 1136-1146.

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Official URL: http://edoc.unibas.ch/dok/A6006177

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Phosphoinositide 3-kinase gamma (PI3Kgamma) plays a fundamental role in mediating leukocyte migration to inflammation sites. However, the downstream cytoplasmic events triggered by its signaling activity are still largely obscure. To address this issue, tyrosine and serine/threonine phosphorylated proteins of chemokine-stimulated WT or PI3Kgamma-null macrophages were investigated. Among the proteins analyzed, the intermediate filament vimentin was found as a downstream effector of the PI3Kgamma signaling pathway. Specific analysis of the phosphorylation state of vimentin in macrophages showed that this protein becomes rapidly phosphorylated in both tyrosine and serine residues upon chemokine stimulation. In the absence of PI3Kgamma or the kinase activity of PI3Kgamma (PI3Kgamma(KD/KD)), phosphorylation of vimentin was reduced. PI3Kgamma-null macrophages displayed impaired chemokine-driven vimentin fiber disassembly as well as reduced ability to transmigrate across endothelial cells. While WT macrophages infected with a vimentin mutant resistant to N-terminal serine phosphorylation showed a reduction in transendothelial migration, infection of PI3Kgamma-null macrophages with a vimentin mutant mimicking serine phosphorylation of N-terminal residues rescued the transendothelial migration defect. These results define vimentin N-terminal phosphorylation and fiber reorganization as a target of chemokine-dependent PI3Kgamma signaling in leukocytes.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Biochemistry and Genetics > Cancer- and Immunobiology (Wymann)
UniBasel Contributors:Wymann, Matthias P.
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Verl. Chemie
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:01 Mar 2013 11:14
Deposited On:01 Mar 2013 11:12

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