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NOD Mice Having a Lyn Tyrosine Kinase Mutation Exhibit Abnormal Neutrophil Chemotaxis
Author(s) -
Wu Yue,
Hannigan Michael,
Zhan Lijun,
Madri Joseph A.,
Huang ChiKuang
Publication year - 2017
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.25583
Subject(s) - lyn , nod , chemotaxis , autophosphorylation , tyrosine phosphorylation , tyrosine , biology , phosphorylation , tyrosine kinase , chemistry , microbiology and biotechnology , immunology , proto oncogene tyrosine protein kinase src , signal transduction , receptor , biochemistry , protein kinase a , gene
Neutrophils from NOD (Non‐Obese Diabetic) mice exhibited reduced migration speed, decreased frequency of directional changes, and loss of directionality during chemotaxis (compared to wild‐type [WT] C57BL/6 mice). Additionally, F‐actin of chemotaxing NOD neutrophils failed to orient toward the chemoattractant gradient and NOD neutrophil adhesion was impaired. A point mutation near the autophosphorylation site of Lyn in NOD mice was identified. Point mutations of G to A (G1412 in LynA and G1199 in LynB) cause a change of amino acid E393 (glutamic acid) to K (lysine) in LynA (E 393 →K) (E 372 of LynB), affecting fMLP‐induced tyrosine phosphorylation. These data indicate that the Lyn mutation in NOD neutrophils is likely responsible for dysregulation of neutrophil adhesion and directed migration, implying the role of Lyn in modulating diabetic patient's susceptibility to bacterial and fungal infections. J. Cell. Physiol. 232: 1689–1695, 2017. © 2016 Wiley Periodicals, Inc.