Differential regulation of immediate early gene expression in preadipocytecells through multiple signaling pathways

Using digoxigenin (DIG)-based differential hybridization, a series of immed iate early genes (IEG) was identified following the adipogenic stimulation in 3T3-L1 preadipocyte cells. Most of the known IEGs were identified as wel l as new members such as zf9 and Stra13. To delineate possible signaling pa thways accounting for these gene expression, a subset of specific kinase in hibitors, SB203580, PD98059, rapamycin, LY294002, and Ro-32-0432, which inh ibit p38 (HOG), MEK (MAPKK), S6 kinase, PI3 kinase, and protein kinase C (P KC), respectively, were employed. The IEGs were classified into three categ ories according to their susceptibility to the inhibitors. Expression of th e first group (c-fos, jun-B, egr-1, tis11, tis21, thrombospondin-1, erp, th yroid hormone receptor [N-10] cyr61, and zf9) was mainly dependent on PKC a nd MEK pathways, while that of the second class (gene33 and tis10) exhibite d an additional dependence on PI3 kinase pathways. The third one (Id-3, gly 96, and Stra13) was characterized in that none of these inhibitors interfer ed with gene expression. Our results suggest that the induction of IEGs by the adipogenic stimuli is mediated by common as well as distinct signaling pathways. (C) 1999 Academic Press.