title: Expression and tyrosine phosphorylation of Crk-associated substrate lymphocyte type (Cas-L) protein in human neutrophils.
abstract: Crk-associated substrate lymphocyte type (Cas-L) protein, also known as human enhancer of filamentation 1 (Hef1) or neural precursor cell-expressed, developmentally down-regulated gene 9 (Nedd9), belongs to the Cas family of adapter proteins, which are involved in integrin signaling. Previous reports showed that Cas-L is expressed preferentially in lymphocytes and epithelial cells. Cas-L mediates signals from integrins, T-cell receptors, B-cells receptors, and transforming growth factor beta, leading to cell movement and cell division. Here, we report the expression of Cas-L in neutrophils. Cas-L was tyrosine-phosphorylated when human neutrophils were stimulated by fMLP, tumor necrosis factor-alpha (TNF), or lipopolysaccharide. The tyrosine phosphorylation of Cas-L in fMLP- or TNF- stimulated neutrophils was further enhanced by adhesion of the cells to their substrates. Cas-L was found to be localized at focal adhesions in stimulated neutrophils based on immunofluorescence microscopy. These findings suggest that Cas-L is one of the targets of inflammatory cytokines and is also modulated by cell adhesion process in neutrophils.
authors.affiliation: 21st Century Center of Excellence (COE) Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nakamoto
authors.forename: Sachiko
authors.initials: S
authors.lastname: Seo
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Sakai
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kato
authors.forename: Haruo
authors.initials: H
authors.lastname: Kutsuna
authors.forename: Mineo
authors.initials: M
authors.lastname: Kurokawa
authors.forename: Masaki
authors.initials: M
authors.lastname: Noda
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Miyasaka
authors.forename: Seiichi
authors.initials: S
authors.lastname: Kitagawa
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D002448:Cell Adhesion; D002460:Cell Line; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D019000:Phosphotyrosine / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D008070:Lipopolysaccharides; C099942:NEDD9 protein, human; D010750:Phosphoproteins; D014409:Tumor Necrosis Factor-alpha; D019000:Phosphotyrosine