Bacterial LPS and IFN-gamma trigger the tyrosine phosphorylation of vav in macrophages: evidence for involvement of the hck tyrosine kinase

We and others have previously reported that tyrosine kinases play key roles in the activation of macrophages by both bacterial lipopolysaccharide (LPS) and interferon‐γ (IFN‐γ). However, little is known regarding the substrates of tyrosine phosphorylation that mediate macrophage activation and the resultant production of inflammatory mediators. In lymphocytes and other hematopoietic lineages, tyrosine phosphorylation of the proto‐oncogene vavappears to be an essential component of cell activation. In this study, we demonstrate that both LPS and rIFN‐γ trigger the prompt, dose‐dependent tyrosine phosphorylation of vavin murine RAW 264.7 macrophages. In addition, vavis physically associated with the src‐related kinase hckin murine macrophages, and antisense oligonucleotides specific for murine hckblock both LPS and rIFN‐γ‐mediated vavphosphorylation. These findings suggest that hckprobably mediates vavtyrosine phosphorylation during macrophage activation and that LPS and rIFN‐γ‐mediated signaling pathways partially overlap. J. Leukoc. Biol. 62: 859–874; 1997.