First Author | Casals-Casas C | Year | 2009 |
Journal | Eur J Immunol | Volume | 39 |
Issue | 7 | Pages | 1902-13 |
PubMed ID | 19585511 | Mgi Jnum | J:150260 |
Mgi Id | MGI:3850251 | Doi | 10.1002/eji.200839037 |
Citation | Casals-Casas C, et al. (2009) CREB and AP-1 activation regulates MKP-1 induction by LPS or M-CSF and their kinetics correlate with macrophage activation versus proliferation. Eur J Immunol 39(7):1902-1913 |
abstractText | MAPK phosphatase-1 (MKP-1) is a protein phosphatase that plays a crucial role in innate immunity. This phosphatase inactivates ERK1/2, which are involved in two opposite functional activities of the macrophage, namely proliferation and activation. Here we found that although macrophage proliferation and activation induce MKP-1 with different kinetics, gene expression is mediated by the proximal promoter sequences localized between -380 and -180 bp. Mutagenesis experiments of the proximal element determined that CRE/AP-1 is required for LPS- or M-CSF-induced activation of the MKP-1 gene. Moreover, the results from gel shift analysis and chromatin immunoprecipitation indicated that c-Jun and CREB bind to the CRE/AP-1 box. The distinct kinetics shown by M-CSF and LPS correlates with the induction of JNK and c-jun, as well as the requirement for Raf-1. The signal transduction pathways that activate the induction of MKP-1 correlate kinetically with induction by M-CSF and LPS. |