Journal
JOURNAL OF LEUKOCYTE BIOLOGY
Volume 93, Issue 4, Pages 611-622Publisher
WILEY
DOI: 10.1189/jlb.1012487
Keywords
membrane protrusion; HL-60; F-actin; acute inflammation; PMNs; cytoskeletal rearrangement
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Funding
- National Natural Science Foundation of China [30971498, 81071726, 31271509]
- National Basic Research Program of China [2010CB529704]
- Natural Science Foundation of Jilin Province [201115165, 201201143]
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The recruitment and migration of neutrophils are critical for innate immunity and acute inflammatory responses. However, the mechanism that regulates the recruitment and migration of neutrophils has not been well characterized. We here reveal a novel function of c-Abl kinase in regulating neutrophil migration. Our results demonstrate that c-Abl kinase is required for neutrophil recruitment in vivo and migration in vitro, and the inhibition of c-Abl kinase activity has a significant impact on neutrophil migratory behavior. Moreover, c-Abl kinase activation depends on beta 2 integrin engagement, and the activated c-Abl kinase further regulates actin polymerization and membrane protrusion dynamics at the extended leading edges during neutrophil migration. In addition, we identify the Rho GEF Vav1 as a major downstream effector of c-Abl kinase. The C-terminal SH3-SH2-SH3 domain and proline-rich region of Vav1 are required for its interaction with c-Abl kinase, and c-Abl kinase probably regulates the activity of Vav1 by direct phosphorylation at Tyr-267 in the DH domain. Together, these results indicate that c-Abl kinase plays a critical role in beta 2 integrin-dependent neutrophil migration by regulating Vav1 activity. J. Leukoc. Biol. 93: 611-622; 2013.
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