Tyrosine phosphorylation of p38 but not extracellular signal-regulated kinase in normal human neutrophils stimulated by tumor necrosis factor: comparative study with granulocyte-macrophage colony-stimulating factor.
We investigated the cytokine-specific involvement of two members of the microtubule-associated protein kinase family, extracellular signal-regulated kinase (ERK)(1 and 2) and p38, in normal human neutrophils. Both tumor necrosis factor (TNF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) induced tyrosine phosphorylation of a 42-kDa protein in human neutrophils, though the time course of its phosphorylation and its band pattern in electrophoresis differed for each of the cytokines. In addition, GM-CSF, but not TNF, induced a mobility shift of 42-kDa ERK2 in human neutrophils. By using immunoprecipitation followed by immunoblotting, we clarified that GM-CSF, but not TNF, induced tyrosine phosphorylation of ERK2 and that TNF, but not GM-CSF, induced tyrosine phosphorylation of p38. Results of a combined stimulation study showed that tyrosine phosphorylation of ERK2 and that of p38 do not interfere or interact with each other at least in human neutrophils. These results indicate cytokine specific involvement and an independent activating system of ERK and p38 in normal human neutrophils stimulated by two cytokines which share many biological activities in these cells.
Yuo
A
A
Department of Hematology, Research Institute, International Medical Center of Japan, Tokyo.
Okuma
E
E
Kitagawa
S
S
Takaku
F
F
D000328:Adult; D015153:Blotting, Western; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology*; D010766:Phosphorylation; D011233:Precipitin Tests; D015398:Signal Transduction / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014443:Tyrosine / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases
D014409:Tumor Necrosis Factor-alpha; D014443:Tyrosine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases