Tumor necrosis factor-alpha initiated signal transduction in 3T3-L1 adipocytes

Examination of the ability of tumor necrosis factor-alpha (TNF) to activate both the p44/42 and p38 MAP kinase cascades in fully differentiated 3T3-L1 adipocytes indicated a rapid MEK1/2-dependent activation of p44/42 MAP kin ase. Use of the MEK1/2 inhibitor PD98059 indicated that this pathway at lea st in part was responsible for nuclear localization of the transcription fa ctor NF-kappa B. The stress/ cytokine-activated p38 NAP kinase was observed to be constitutively active, and its phosphorylation (activation) status w as not altered with TNF treatment. However, TNF treatment did result in act ivation of the transcription factor, ATF-2, a primary downstream target of p38 MAP kinase. Use of the p38 MAP kinase inhibitors SB202190 and SB202580 did not interfere with the ability of TNF to activate ATF-2, suggesting tha t either the gamma isoform of p38 MAP kinase or a p38-independent pathway w as utilized by TNF to increase the phosphorylated fraction of ATF-2, In pre vious studies we had demonstrated the ability of TNF to suppress the transc ription of the GLUT4 gene. Prevention of activation of either the p44/42 MA P kinase pathway(PD98059) or the p38 MAP kinase pathway (SB202190 and SB202 580) indicated that these pathways did not control GLUT4 transcription. J. Cell. Physiol. 179:58-66, 1999. (C) 1999 Wiley-Liss, Inc.