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Key role of proline‐rich tyrosine kinase 2 in interleukin‐8 (CXCL8/IL‐8)‐mediated human neutrophil chemotaxis
Author(s) -
Di Cioccio Vito,
Strippoli Raffaele,
Bizzarri Cinzia,
Troiani Giulia,
Cervellera Maria Neve,
Gloaguen Isabelle,
Colagrande Antonella,
Cattozzo Elisa Margherita,
Pagliei Sabrina,
Santoni Angela,
Colotta Francesco,
Mainiero Fabrizio,
Bertini Riccardo
Publication year - 2004
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2004.01822.x
Subject(s) - chemotaxis , tyrosine phosphorylation , proto oncogene tyrosine protein kinase src , interleukin 8 , microbiology and biotechnology , tyrosine kinase , protein tyrosine phosphatase , receptor tyrosine kinase , phosphorylation , signal transduction , biology , chemistry , cancer research , biochemistry , receptor , inflammation , immunology
Summary 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.