Details

Autor(en) / Beteiligte

• Cohen-Hillel, E
• Mintz, R
• Meshel, T
• Garty, B.-Z
• Ben-Baruch, A

Titel

Cell migration to the chemokine CXCL8: Paxillin is activated and regulates adhesion and cell motility

Ist Teil von

• Cellular and molecular life sciences : CMLS, 2009-03, Vol.66 (5), p.884-899

Ort / Verlag

Basel: Basel : Birkhäuser-Verlag

Erscheinungsjahr

2009

Quelle

MEDLINE

Beschreibungen/Notizen

• The chemokine CXCL8 is a powerful inducer of directional cell motility, primarily during inflammation. In this study, we found that CXCL8 stimulation led to paxillin phosphorylation in normal neutrophils, and that both CXCL8 receptors (CXCR1 and CXCR2) mediated CXCL8-induced paxillin phosphorylation. In CXCR2-transfected cells, the process depended on Gαi and Gαs coupling to CXCR2. Dominant negative (DN) paxillin increased CXCL8-induced adhesion and migration, indicating that endogenous paxillin keeps migration at submaximal levels. Furthermore, using activating antibodies to β1 integrins, analyses with focal adhesion kinase (FAK) DN variant (FRNK) and co-immunoprecipitations of FAK and paxillin, we found that β1 integrin ligation cooperates with CXCL8-induced stimulation, leading to FAK activation and thereafter to FAK-mediated paxillin phosphorylation. Our findings indicate that paxillin keeps directional motility at a restrained magnitude, and suggest that perturbations in its activation may lead to chemotactic imbalance and to pathological conditions associated with excessive or reduced leukocyte migration.