INTERLEUKIN-1 INDUCED SIGNALING - 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 kinase s 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 contr ol levels and increased again after 15 min of interleukin-1 stimulatio n, Inhibition by okadaic acid of serine/threonine specific phosphatase s resulted in a marked increase in interleukin-1 stimulated MEK and MA P kinase activities. Elevation by interleukin-1 of the specific activi ties of MEK and MAP kinases correlated with suppression of serine/thre onine 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 p rotein kinases and repressed phosphoprotein phosphatase 2A in interleu kin-1 stimulated HeLa cells.