Interleukin-13 induces rapid tyrosine phosphorylation and activation of Raf-1 kinase in human monocytic progenitor cell line U937.
IL-13 is a pleiotropic cytokine produced by Th0, Th1-like, and CD8 T cells in response to antigen stimulation. Its biological effects include suppression of cytotoxic activity of monocytes/macrophages and suppression of pro-inflammatory cytokine production. However, the mechanism of IL-13 remains unknown. In this study we investigated the effects of rhIL-13 on tyrosine phosphorylation in U937 monocytic progenitor cells by immunoblotting and immunocomplex kinase assays. We demonstrate that rhIL-13 stimulates dose-dependent tyrosine phosphorylation of several proteins of Mr. 93, 80, 74, 49.5, 42, 30, 22 and 18 kDa within 30 sec. The effect of IL-13 was blocked by the tyrosine kinase inhibitor erbstatin. Furthermore, IL-13 induces tyrosine phosphorylation and rapid activation of raf-1 kinase. These findings provide the first evidence that the mechanism of IL-13 involves rapid tryrosine phosphorylation and activation of raf-1 serine/threonine kinase.
Adunyah
S E
SE
Dept. of Biochemistry, Meharry Medical College, Nashville, TN.
Pegram
M L
ML
Cooper
R S
RS
D015153:Blotting, Western; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation; D006801:Humans; D006873:Hydroquinones / Q000494:pharmacology; D018793:Interleukin-13 / Q000494:pharmacology*; D007700:Kinetics; D009000:Monocytes; D010750:Phosphoproteins / Q000302:isolation & purification / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019908:Proto-Oncogene Proteins c-raf; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism
D006873:Hydroquinones; D018793:Interleukin-13; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D019000:Phosphotyrosine; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; C048212:erbstatin