Key role of proline-rich tyrosine kinase 2 in interleukin-8 (CXCL8/IL-8)-mediated human neutrophil chemotaxis

Immunology. 2004 Apr;111(4):407-15. doi: 10.1111/j.1365-2567.2004.01822.x.


The signalling pathways leading to CXCL8/IL-8-induced human neutrophil migration have not been fully characterized. The present study demonstrates that CXCL8 induces tyrosine phosphorylation as well as enzymatic activity of proline-rich tyrosine kinase 2 (Pyk2), a non-receptor protein tyrosine kinase (PTK), in human neutrophils. Induction of Pyk2 tyrosine phosphorylation by CXCL8 is regulated by Src PTK activation, whereas it is unaffected by phosphatidylinositol 3-kinase activation. Inhibition of Pyk2 activation by PP1, a Src PTK inhibitor, is paralleled by the inhibition of CXCL8-mediated neutrophil chemotaxis. Among CXCL8 receptors, Src protein tyrosine kinase activation selectively regulates CXCR1-mediated polymorphonuclear neutrophil (PMN) chemotaxis. Overexpression of PykM, the kinase-dead mutant of Pyk2, blocks CXCL8-induced chemotaxis of HL-60-derived PMN-like cells, thus pinpointing the key role of Pyk2 in CXCL8-induced chemotaxis.

MeSH terms

  • Cells, Cultured
  • Chemokines, CXC / immunology*
  • Chemotaxis, Leukocyte / immunology*
  • Focal Adhesion Kinase 2
  • HL-60 Cells
  • Humans
  • Intercellular Signaling Peptides and Proteins / immunology*
  • Interleukin-8 / immunology*
  • Neutrophils / enzymology
  • Neutrophils / immunology*
  • Phosphorylation
  • Protein-Tyrosine Kinases / immunology*
  • Protein-Tyrosine Kinases / metabolism
  • Tyrosine / metabolism


  • Chemokines, CXC
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-8
  • Tyrosine
  • Protein-Tyrosine Kinases
  • Focal Adhesion Kinase 2