title: -NOD Mice Having a Lyn Tyrosine Kinase Mutation Exhibit Abnormal Neutrophil Chemotaxis.
abstract: 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 (E393→K) (E372of 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.
authors: Department of Immunology, University of Connecticut Health Center, Farmington, Connecticut.|Department of Pathology, Yale University School of Medicine, New Haven, Connecticut.
authors: Yue
authors: Y
authors: Wu
authors: Department of Immunology, University of Connecticut Health Center, Farmington, Connecticut.
authors: Michael
authors: M
authors: Hannigan
authors: Department of Immunology, University of Connecticut Health Center, Farmington, Connecticut.
authors: Lijun
authors: L
authors: Zhan
authors: Department of Pathology, Yale University School of Medicine, New Haven, Connecticut.
authors: Joseph A
authors: JA
authors: Madri
authors: Department of Immunology, University of Connecticut Health Center, Farmington, Connecticut.
authors: Chi-Kuang
authors: CK
authors: Huang
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D005340:Fibrinogen / Q000494:pharmacology; D005353:Fibronectins / Q000494:pharmacology; D008297:Male; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D050505:Mutant Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000378:metabolism; D058105:Polymerization / Q000187:drug effects; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D000199:Actins; D005353:Fibronectins; D050505:Mutant Proteins; D019000:Phosphotyrosine; D009240:N-Formylmethionine Leucyl-Phenylalanine; D005340:Fibrinogen; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases