Expression and tyrosine phosphorylation of Crk-associated substrate lymphocyte type (Cas-L) protein in human neutrophils.
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.
Nakamoto
Tetsuya
T
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.
Seo
Sachiko
S
Sakai
Ryuichi
R
Kato
Takayuki
T
Kutsuna
Haruo
H
Kurokawa
Mineo
M
Noda
Masaki
M
Miyasaka
Nobuyuki
N
Kitagawa
Seiichi
S
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
D048868:Adaptor Proteins, Signal Transducing; D008070:Lipopolysaccharides; C099942:NEDD9 protein, human; D010750:Phosphoproteins; D014409:Tumor Necrosis Factor-alpha; D019000:Phosphotyrosine