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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. J. Cell. Biochem. 105: 121–128, 2008. © 2008 Wiley‐Liss, Inc.