Key role of proline-rich tyrosine kinase 2 in interleukin-8 (CXCL8/IL-8)-mediated human neutrophil chemotaxis.
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.
Di Cioccio
Vito
V
Dompé S.p.A., L'Aquila, Italy.
Strippoli
Raffaele
R
Bizzarri
Cinzia
C
Troiani
Giulia
G
Cervellera
Maria Neve
MN
Gloaguen
Isabelle
I
Colagrande
Antonella
A
Cattozzo
Elisa Margherita
EM
Pagliei
Sabrina
S
Santoni
Angela
A
Colotta
Francesco
F
Mainiero
Fabrizio
F
Bertini
Riccardo
R
D002478:Cells, Cultured; D019743:Chemokines, CXC / Q000276:immunology*; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D051418:Focal Adhesion Kinase 2; D018922:HL-60 Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000276:immunology*; D016209:Interleukin-8 / Q000276:immunology*; D009504:Neutrophils / Q000201:enzymology / Q000276:immunology*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000276:immunology* / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D019743:Chemokines, CXC; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D051418:Focal Adhesion Kinase 2