THE ACTIVATION OF DISTINCT MITOGEN-ACTIVATED PROTEIN-KINASE CASCADES IS REQUIRED FOR THE STIMULATION OF 2-DEOXYGLUCOSE UPTAKE BY INTERLEUKIN-1 AND INSULIN-LIKE GROWTH-FACTOR-I IN KB CELLS

The uptake of 2-deoxyglucose into KB cells was stimulated about 2-fold by interleukin-l (IL1), anisomycin or insulin-like growth factor-1 (IGF1), Stimulation by IL1 and anisomycin was prevented by SE 203580, a specific inhibitor of the mitogen-activated protein (MAP) kinase homologue termed 're-activating kinase' [RK; also known as p38, p40 and CSBP (cytokine synthesis anti-inflammatory-drug-binding protein)], but was unaffected by PD 98059, a specific inhibitor of the activation of the classical MAP kinase pathway. In contrast, the stimulation of 2-deoxyglucose uptake by IGF1 was blocked by PD 98059 and unaffected by SE 203580. Consistent with these observations, IL1 and anisomycin were potent activators of MAP kinase-activated protein (MAPKAP) kinase-2, a physiological substrate of RK, whereas IGF1 was only a very weak activator of MAPKAP kinase-2. Conversely, IGF1 was a stronger activator of p42 MAP kinase than IL1 or anisomycin. These results imply that the activation of distinct MAP kinase pathways is required for the stimulation of glucose transport by IL1/anisomycin and IGF1 in KB cells, and suggest that the combined use of SE 203580 and PD 98059 is a powerful new approach to explore the roles of different MAP kinase cascades in cell regulation.