Nakamoto Tetsuya, Seo Sachiko, Sakai Ryuichi, Kato Takayuki, Kutsuna Haruo, Kurokawa Mineo, Noda Masaki, Miyasaka Nobuyuki, Kitagawa Seiichi
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.
J Cell Biochem. 2008 Sep 1;105(1):121-8. doi: 10.1002/jcb.21799.
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.
Crk相关底物淋巴细胞型（Cas-L）蛋白，也被称为丝状化增强因子1（Hef1）或神经前体细胞表达、发育下调基因9（Nedd9），属于衔接蛋白的Cas家族，该家族参与整合素信号传导。先前的报道表明，Cas-L在淋巴细胞和上皮细胞中优先表达。Cas-L介导来自整合素、T细胞受体、B细胞受体和转化生长因子β的信号，导致细胞移动和细胞分裂。在此，我们报道了Cas-L在中性粒细胞中的表达。当人中性粒细胞受到fMLP、肿瘤坏死因子-α（TNF）或脂多糖刺激时，Cas-L发生酪氨酸磷酸化。细胞与底物黏附进一步增强了fMLP或TNF刺激的中性粒细胞中Cas-L的酪氨酸磷酸化。基于免疫荧光显微镜观察，发现Cas-L定位于受刺激中性粒细胞的黏着斑。这些发现表明，Cas-L是炎性细胞因子的靶标之一，并且在中性粒细胞中也受细胞黏附过程的调节。
