Interleukin-1 induced signalling: biphasic activation of mitogen-activated protein kinase kinase and mitogen-activated protein kinases in HeLa cells. Involvement of phosphoprotein phosphatases.
Results of this study document a biphasic activation of protein kinases of the MAP kinase cascade-MEK and MAP kinases-upon interleukin-1 stimulation in human HeLa cells. The specific activities of both MEK and MAP kinases were increased within 1 min, declined rapidly to control levels and increased again after 15 min of interleukin-1 stimulation. Inhibition by okadaic acid of serine/threonine specific phosphatases resulted in a marked increase in interleukin-1 stimulated MEK and MAP kinase activities. Elevation by interleukin-1 of the specific activities of MEK and MAP kinases correlated with suppression of serine/threonine phosphatases in the late phase of stimulation. The data indicate, that enhanced phosphorylation of cellular proteins by enzymes of the MAP kinase cascade might represent a fine balance between activated protein kinases and repressed phosphoprotein phosphatase 2A in interleukin-1 stimulated HeLa cells.
Appel
A
A
Institute of Molecular Pharmacology, Medical School Hannover, Germany.
Kracht
M
M
Petersen
K
K
Resch
K
K
Szamel
M
M
D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D004789:Enzyme Activation; D006367:HeLa Cells; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D048728:MAP Kinase Kinase Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D054648:Protein Phosphatase 2; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
D007375:Interleukin-1; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048728:MAP Kinase Kinase Kinase 1; C482576:MAP3K1 protein, human; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2