CXCL8-induced FAK phosphorylation via CXCR1 and CXCR2: Cytoskeleton- and integrin-related mechanisms converge with FAK regulatory pathways in a receptor-specific manner

Efrat Cohen-Hillel, Ilana Yron, Tsipi Meshel, Gali Soria, Hila Attal, Adit Ben-Baruch

Research output: Contribution to journalArticlepeer-review

Abstract

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 β-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.

Original languageEnglish
Pages (from-to)1-16
Number of pages16
JournalCytokine
Volume33
Issue number1
DOIs
StatePublished - 7 Jan 2006

Keywords

  • CXCL8
  • CXCR1
  • CXCR2
  • Focal adhesion kinase

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