Lyn, one of the Src-family tyrosine kinases expressed in phagocytes, plays an important role in beta2 integrin-signalling pathways in opsonized zymosan-activated macrophage-like U937 cells

Abstract

We have investigated the contribution of Hck, Lyn and Fgr, highly expressed Src family tyrosine kinases (SFKs) in signalling pathways in opsonized zymosan (OZ)-activated phagocytes by using short interfering RNAs (siRNAs). Treatment of macrophage-like U937 cells with the siRNAs targeted to these transcripts decreased the protein content of each kinase to less than half that of untreated cells. Among these siRNAs, siRNA targeted to Lyn was the most effective in diminishing two kinds of phagocyte functions, that is oxidative burst and phagocytosis. Phosphorylation of c-Cbl, a multidomain adaptor protein in the beta2 integrin-signalling pathway, was also largely inhibited by treatment with siRNA to Lyn. Thus, the results with siRNAs highly specific for Hck, Lyn and Fgr suggested that, among these three SFKs, Lyn plays the most important role in signalling pathways downstream of beta2 integrins in OZ-stimulated phagocytes.