|Title||Activation of extracellular signal-regulated kinases and CREB/ATF-1 mediate the expression of CCAAT/enhancer binding proteins beta and -delta in preadipocytes.|
|Publication Type||Journal Article|
|Year of Publication||2001|
|Authors||Belmonte N, Phillips BW, Massiera F, Villageois P, Wdziekonski B, Saint-Marc P, Nichols J, Aubert J, Saeki K, Yuo A, Narumiya S, Ailhaud G, Dani C|
|Date Published||2001 Nov|
|Keywords||Activating Transcription Factor 1, Adipocytes, Animals, CCAAT-Enhancer-Binding Protein-beta, CCAAT-Enhancer-Binding Protein-delta, CCAAT-Enhancer-Binding Proteins, Cells, Cultured, Cyclic AMP Response Element-Binding Protein, Cyclic AMP-Dependent Protein Kinases, DNA-Binding Proteins, Enzyme Activation, Epoprostenol, Gene Expression Regulation, Leukemia Inhibitory Factor Receptor alpha Subunit, Mice, Mice, Inbred Strains, Mice, Mutant Strains, Mitogen-Activated Protein Kinases, Phosphorylation, Receptors, Cytokine, Receptors, Epoprostenol, Receptors, OSM-LIF, Receptors, Prostaglandin, Transcription Factors, Transfection|
The essential role of CCAAT/enhancer binding proteins (C/EBPs) beta and delta for adipocyte differentiation has been clearly established. In preadipocytes, their expression is up-regulated by the activation of leukemia inhibitory factor receptor (LIF-R) and prostacyclin receptor (IP-R) via the extracellular signal-regulated kinase (ERK) pathway and cAMP production, respectively. However, the molecular mechanisms by which LIF and prostacyclin-induced signals are propagated to the nucleus and the transcription factors mediating ERK and cAMP-induced C/EBP gene expression were unknown. Here we report that both pathways share cAMP responsive element binding protein/activation transcription factor 1 (CREB/ATF-1) as common downstream effectors. LIF-R and IP-R activation induced binding of CREB and/or ATF-1 to C/EBP promoters and CREB-dependent transcription. Expression of dominant negative forms of CREB dramatically reduced the LIF- and prostacyclin-stimulated C/EBP beta and C/EBP delta expression. Upon stimulation of the IP-R, the ERK pathway was activated in a PKA-dependent manner. ERK activation by the PKA pathway was not required for CREB/ATF-1 phosphorylation but rather was necessary for CREB-dependent up-regulation of C/EBPs expression. Our findings suggest that ERK activation is required for CREB transcriptional activity, possibly by recruitment of a coactivator.
|Alternate Journal||Mol. Endocrinol.|