c-Abl tyrosine kinase regulates neutrophil crawling behavior under fluid shear stress via Rac/PAK/LIMK/cofilin signaling axis.
J Cell Biochem
; 119(3): 2806-2817, 2018 03.
Article
em En
| MEDLINE
| ID: mdl-29058761
ABSTRACT
The excessive recruitment and improper activation of polymorphonuclear neutrophils (PMNs) often induces serious injury of host tissues, leading to inflammatory disorders. Therefore, to understand the molecular mechanism on neutrophil recruitment possesses essential pathological and physiological importance. In this study, we found that physiological shear stress induces c-Abl kinase activation in neutrophils, and c-Abl kinase inhibitor impaired neutrophil crawling behavior on ICAM-1. We further identified Vav1 was a downstream effector phosphorylated at Y174 and Y267. Once activated, c-Abl kinase regulated the activity of Vav1, which further affected Rac1/PAK1/LIMK1/cofilin signaling pathway. Here, we demonstrate a novel signaling function and critical role of c-Abl kinase during neutrophil crawling under physiological shear by regulating Vav1. These findings provide a promising treatment strategy for inflammation-related disease by inactivation of c-Abl kinase to restrict neutrophil recruitment.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Movimento Celular
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Proteínas Proto-Oncogênicas c-abl
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Proteínas rac1 de Ligação ao GTP
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Resistência ao Cisalhamento
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Fatores de Despolimerização de Actina
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Quinases Lim
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Quinases Ativadas por p21
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Neutrófilos
Tipo de estudo:
Prognostic_studies
Limite:
Female
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Humans
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Male
Idioma:
En
Revista:
J Cell Biochem
Ano de publicação:
2018
Tipo de documento:
Article