TNF is a cytokine secreted by macrophages and adipocytes that contributes to the low grade inflammation and insulin resistance observed in obesity. TNF signaling decreases PPAR and GLUT4 glucose transporter expression in adipocytes, impairing insulin action, and this is mediated in part by the yeast Ste20 protein kinase ortholog Map4k4. Here we show that Map4k4 expression is selectively upregulated by TNF, while the expression of the protein kinases JNK1/2, ERK1/2, p38 SAP kinase, MKK4 and MKK7 shows little or no response. Furthermore, the cytokines IL-1 and IL-6 as well as LPS fails to increase Map4k4 mRNA levels in cultured adipocytes under conditions where TNF elicits a 3 fold effect. Using agonistic and antagonistic antibodies and siRNA against TNF receptor 1 (TNFR1) and TNF receptor 2 (TNFR2), we show that TNFR1, but not TNFR2 mediates the increase in Map4k4 expression. TNFR1, but not TNFR2, also mediates a potent effect of TNF on the phosphorylation of JNK1/2 and p38 SAP kinase and their downstream transcription factor substrates cJUN and ATF2. RNAi-based depletion of cJUN and ATF2 attenuated TNF action on Map4k4 mRNA expression. Consistent with this concept, the phosphorylation of ATF2, along with the expression and phosphorylation of cJUN by TNF signaling was more robust and prolonged compared to that of IL-1, which failed to modulate Map4k4. These data reveal that TNF selectively stimulates the expression of a key component of its own signaling pathway, Map4k4, through a TNFR1-dependent mechanism that targets the transcription factors cJUN and ATF2.