CXCL8-induced FAK phosphorylation via CXCR1 and CXCR2: Cytoskeleton- and integrin-related mechanisms converge with FAK regulatory pathways in a receptor-specific manner
| Autor: | Efrat Cohen-Hillel, Tsipi Meshel, Gali Soria, Hila Attal, Adit Ben-Baruch, Ilana Yron |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
musculoskeletal diseases
Integrins Immunology Integrin macromolecular substances Biology Transfection Microtubules Models Biological Biochemistry Receptors Interleukin-8B Cell Line Receptors Interleukin-8A Focal adhesion Cell Movement Humans Immunology and Allergy CXC chemokine receptors Phosphorylation Cytoskeleton Molecular Biology Actin G protein-coupled receptor Microscopy Confocal Interleukin-8 Hematology Cell biology Focal Adhesion Kinase 1 Cell Migration Inhibition biology.protein Signal transduction Signal Transduction |
| Zdroj: | Cytokine. 33:1-16 |
| ISSN: | 1043-4666 |
| Popis: | CXCL8 is a potent chemokine, inducing focal adhesion kinase (FAK) phosphorylation, and migration via a FAK-mediated pathway. Since, unlike growth factors, chemokines directly control integrins and cytoskeleton rearrangements, we determined whether these elements regulate CXCL8-induced FAK phosphorylation. The analysis intentionally dissociated between the CXCL8 receptors CXCR1 and CXCR2. In both CXCR1- and CXCR2-expressing cells, actin and microtubules were required for CXCL8-induced FAK phosphorylation, and CXCL8-induced cell spreading was accompanied by concordant re-localization of FAK with actin and beta-tubulin. The phosphorylation of five FAK sites depended on intact actin filaments and microtubules. While in CXCR2-expressing cells FAK phosphorylation was adhesion-dependent and was stimulated by fibronectin, in CXCR1-expressing cells FAK phosphorylation was adhesion-independent. Of note, even in the absence of integrin stimulation, the CXCL8-induced phosphorylation of FAK in CXCR1-expressing cells required cytoskeletal elements. CXCL8-induced migration in both cell types was highly reliant on actin filaments, but only the migration of CXCR1-expressing cells was fully dependent on microtubules. Overall, several aspects of CXCL8-induced FAK phosphorylation and migration are regulated in a receptor-specific manner. These observations lay the basis for future investigation of the equilibrium between CXCR1 and CXCR2 in cells expressing both receptors together, such as neutrophils, endothelial cells and tumor cells. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect