Fc gamma receptor cross-linking activates p42, p38, and JNK/SAPK mitogen-activated protein kinases in murine macrophages: role for p42MAPK in Fc gamma receptor-stimulated TNF-alpha synthesis.
Fc gamma R cross-linking on murine macrophages resulted in the activation of mitogen-activated protein kinase (MAPK) family members p42MAPK, p38, and c-Jun NH2-terminal kinase (JNK)/stress-activated protein kinase (SAPK). The temporal pattern of activation was distinct for each kinase. p42MAPK activation peaked at 5 min after receptor cross-linking, while peak p38 activity occurred 5 to 10 min later. Maximal JNK/SAPK activation occurred 20 min after Fc gamma R cross-linking. The selective MAPK/extracellular signal-regulated kinase-1 (MEK-1) inhibitor PD 098059 inhibited activation of p42MAPK induced by Fc gamma R cross-linking, but not p38 or JNK/SAPK activation. PD 098059 also inhibited the synthesis of TNF-alpha induced by Fc gamma R cross-linking (IC50 approximately 0.1 microM). Together, these results suggest that 1) the activation of MAPKs may play a role in Fc gammaR signal transduction, and 2) the activation of p42MAPK is necessary for Fc gamma R cross-linking-induced TNF-alpha synthesis.
Rose
D M
DM
Division of Basic Sciences, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206, USA.
Winston
B W
BW
Chan
E D
ED
Riches
D W
DW
Gerwins
P
P
Johnson
G L
GL
Henson
P M
PM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism* / Q000502:physiology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology*; D004789:Enzyme Activation / Q000276:immunology; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D008264:Macrophages / Q000201:enzymology*; D051379:Mice; D008809:Mice, Inbred C3H; D019950:Mitogen-Activated Protein Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D011485:Protein Binding / Q000276:immunology; D011494:Protein Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology*; D017452:Receptors, IgG / Q000378:metabolism* / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases
D000911:Antibodies, Monoclonal; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases