c-Abl kinase is required for beta 2 integrin-mediated neutrophil adhesion.
Integrin regulation in neutrophil adhesion is essential for innate immune response. c-Abl kinase is a nonreceptor tyrosine kinase and is critical for signaling transduction from various receptors in leukocytes. Using neutrophils and dHL-60 (neutrophil-like differentiation of HL-60) cells, we show that c-Abl kinase is activated by beta(2) integrin engagement and is required for beta(2) integrin-dependent neutrophil sustained adhesion and spreading. The expression of beta(2) integrin on neutrophils induced by TNF-alpha is not affected by c-Abl kinase inhibitor STI571, suggesting that c-Abl kinase is not involved in TNF-alpha-induced integrin activation. The recruitment of c-Abl kinase to beta(2) integrin is dependent on talin head domain, which constitutively interacts with beta(2) integrin cytoplasmic domain. After activated, c-Abl kinase increases the tyrosine phosphorylation of Vav. The SH3 domain of c-Abl kinase is involved in its interaction with talin and Vav. Thus, c-Abl kinase plays an essential role in the activation of Vav induced by beta(2) integrin ligation and in regulating neutrophil-sustained adhesion and spreading.
Cui
Lingling
L
Institute of Genetics and Cytology, Northeast Normal University, Changchun, People's Republic of China.
Chen
Cuixia
C
Xu
Ting
T
Zhang
Juechao
J
Shang
Xin
X
Luo
Jixian
J
Chen
Liang
L
Ba
Xueqing
X
Zeng
Xianlu
X
D018821:CD18 Antigens / Q000378:metabolism / Q000502:physiology*; D002448:Cell Adhesion / Q000276:immunology; D003593:Cytoplasm / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D018375:Neutrophil Activation / Q000276:immunology; D009504:Neutrophils / Q000166:cytology* / Q000201:enzymology / Q000276:immunology*; D017434:Protein Structure, Tertiary; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology; D016608:Talin / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D018821:CD18 Antigens; D016608:Talin; D014409:Tumor Necrosis Factor-alpha; D016315:Proto-Oncogene Proteins c-abl