IL-5 activates a 45-kilodalton mitogen-activated protein (MAP) kinase and Jak-2 tyrosine kinase in human eosinophils.
IL-5 is a member of the hemopoietic cytokine family and has profound effects on the differentiation, survival, migration, and effector function of human eosinophils. Increased tyrosine phosphorylation has been observed as an early event in IL-5 signal transduction in eosinophils; most notably, proteins of 45 and 135 kDa became tyrosine phosphorylated following IL-5 treatment. Some of these phosphotyrosine-containing proteins may represent intermediates in IL-5 signal transduction pathways. This study demonstrates that Jak-2, a tyrosine kinase, is increasingly tyrosine phosphorylated after IL-5 treatment of human eosinophils. Furthermore, we found proteins of 42, 44, and 45 kDa immunoreactive with anti-mitogen-activated protein (MAP) kinase Abs that are expressed in human eosinophils. One of these, the protein of approximately 45 kDa (p45), was tyrosine phosphorylated following treatment of eosinophils with IL-5 and PMA, as seen by anti-phosphotyrosine immunoprecipitation and immunoblotting with anti-MAP kinase Abs. In addition, anti-phosphotyrosine immunoprecipitates of IL-5-treated eosinophils contained enhanced phosphotransferase activity toward a myelin basic protein (MBP) peptide substrate when compared with control-treated eosinophils. In contrast to cytokine-stimulated MAP kinase activation in other cells, there is no evidence of tyrosine phosphorylation or enzymatic activation of p42 MAP kinase in eosinophils after IL-5 treatment. These data suggest that Jak-2 kinase and an activated isoform of MAP kinase, p45, are detected following incubation with IL-5, and may mediate some of this cytokine's effects on eosinophils in a manner unique to the activation pathways previously described for other cells.
Department of Medicine, University of Wisconsin, Madison 53792, USA.
M E
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Bates
P J
PJ
Bertics
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WW
Busse
D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000276:immunology / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D004804:Eosinophils / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D015848:Interleukin-5 / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism*; D053614:Janus Kinase 2; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D008970:Molecular Weight; D010750:Phosphoproteins / Q000096:biosynthesis / Q000302:isolation & purification; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000276:immunology; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000276:immunology / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D013268:Stimulation, Chemical; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D015848:Interleukin-5; D007527:Isoenzymes; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D013755:Tetradecanoylphorbol Acetate