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.
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.
Adachi
Reiko
R
Division of Biosignaling, National Institute of Health Sciences, Setagaya-ku, Tokyo, Japan. akasaka@nihs.go.jp
Suzuki
Kazuhiro
K
D018821:CD18 Antigens / Q000502:physiology*; D002454:Cell Differentiation; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008969:Molecular Sequence Data; D009895:Opsonin Proteins / Q000494:pharmacology; D010586:Phagocytes / Q000378:metabolism*; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000187:drug effects; D050721:Proto-Oncogene Proteins c-cbl / Q000187:drug effects / Q000378:metabolism; D051572:Proto-Oncogene Proteins c-hck / Q000096:biosynthesis / Q000187:drug effects; D034741:RNA, Small Interfering / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*; D013329:Structure-Activity Relationship; D020298:U937 Cells; D015054:Zymosan / Q000494:pharmacology*; D019061:src-Family Kinases / Q000096:biosynthesis* / Q000187:drug effects
D018821:CD18 Antigens; D009895:Opsonin Proteins; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D015054:Zymosan; D050721:Proto-Oncogene Proteins c-cbl; C496631:HCK protein, human; D051572:Proto-Oncogene Proteins c-hck; C060902:lyn protein-tyrosine kinase; C053102:proto-oncogene proteins c-fgr; D019061:src-Family Kinases; C067419:CBL protein, human