Possible role of tyrosine kinase activity in interleukin 4-induced expression of germ-line C epsilon transcripts in a human Burkitt lymphoma B-cell line, DND39.
Despite the recent advances in knowledge of the molecular mechanism by which interleukin-4 (IL-4) induces IgE production, little is known about the signal transduction pathway that leads to this event. This study investigated the signal transduction mechanism responsible for IL-4-induced expression of germ-line C epsilon transcripts with use of a human Burkitt lymphoma B-cell line, DND39, which is known to express germ-line C epsilon transcripts in response to IL-4. On stimulation with IL-4, the generation of inositol triphosphate was observed in the cells. In addition, this generation was associated with activation of phospholipase C-gamma 1 (PLC-gamma 1). Although herbimycin A, a potent inhibitor of tryosine kinase, inhibited IL-4-induced activation of PLC-gamma 1 and generation of inositol triphosphate, direct phosphorylation of PCL-gamma 1 was not determined. Nevertheless, IL-4 stimulation could induce activation of FYN but not LYN kinase, suggesting that additional molecule(s) might link FYN kinase to PLC-gamma 1. Interestingly, herbimycin A almost completely inhibited IL-4-induced expression of germ-line C epsilon transcripts when present during the entire culture period. These results indicate that the induction of germ-line C epsilon transcripts in IL-4-stimulated DND39 cells is essentially dependent on the activation of tyrosine kinase, possibly FYN kinase.
Ikizawa
K
K
Clinical Research Center for Allergy, National Sagamihara Hospital, Kanagawa, Japan.
Kajiwara
K
K
Koshio
T
T
Yanagihara
Y
Y
D001402:B-Lymphocytes / Q000276:immunology; D002051:Burkitt Lymphoma / Q000201:enzymology / Q000276:immunology*; D005786:Gene Expression Regulation; D006801:Humans; D007139:Immunoglobulin epsilon-Chains / Q000235:genetics / Q000378:metabolism*; D015847:Interleukin-4 / Q000502:physiology*; D010716:Phosphatidylinositols / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
D007139:Immunoglobulin epsilon-Chains; D010716:Phosphatidylinositols; D012333:RNA, Messenger; D015847:Interleukin-4; D011505:Protein-Tyrosine Kinases