Interleukin-12 induces tyrosine phosphorylation and activation of 44-kD mitogen-activated protein kinase in human T cells.
Interleukin-12 (IL-12) is a novel cytokine that enhances numerous functional activities of human T cells and natural killer (NK) cells. The present studies were undertaken to characterize some of the early signaling events following IL-12 stimulation of mitogen-activated normal T cells. In these cells, IL-12 induces rapid tyrosine phosphorylation of proteins of 21, 44, and 54 kD. However, IL-12 does not induce tyrosine phosphorylation in normal resting T cells. In conjunction with increased tyrosine phosphorylation of several substrates, IL-12 stimulation resulted in increased in vitro kinase activity of immunoprecipitated tyrosine phosphorylated proteins. The 44-kD protein has been characterized as one isoform of the mitogen-activated protein (MAP) kinase family. Increased tyrosine phosphorylation of MAP kinase following IL-12 stimulation was also associated with enhanced enzymatic activity of this protein in vitro as measured by myelin basic protein phosphotransferase assay. These studies identify MAP kinase as one of the intracellular elements of the IL-12 signaling pathway in human T cells.
Pignata
C
C
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA 02115.
Sanghera
J S
JS
Cossette
L
L
Pelech
S L
SL
Ritz
J
J
D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D018664:Interleukin-12; D007378:Interleukins / Q000494:pharmacology*; D008213:Lymphocyte Activation; D019950:Mitogen-Activated Protein Kinase 1; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism*
D007378:Interleukins; D018664:Interleukin-12; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D019950:Mitogen-Activated Protein Kinase 1