Mice lacking MAP kinase phosphatase-1 have enhanced MAP kinase activity and resistance to diet-induced obesity

Wu, Jiliang; Roth, Rachel J.; Anderson, Ethan J.; Hong, Eun‐Gyoung; Lee, Mi-Kyung; Choi, Cheol Soo; Neufer, P. Darrell; Shulman, Gerald I.; Kim, Jason K.; Bennett, Anton M.

doi:10.1016/j.cmet.2006.05.010

Cited by 195 publications

(237 citation statements)

References 52 publications

Supporting

Mentioning

222

Contrasting

Unclassified

Order By: Relevance

Section: Discussionmentioning

confidence: 79%

“…Moreover, conditions that block MKP-1 induction by M-CSF elongate ERK activity and inhibit proliferation [10,11]. This observation is supported by the finding that mice lacking MKP-1 have enhanced MAPK activity [48].Here we show that transcriptional induction of MKP-1 during macrophage proliferation or activation is mediated by a complex of transcription factors, of which we have identified CREB and c-jun, which bind to a CREB/AP-1 sequence located in the Eur. J. Immunol.…”

mentioning

confidence: 77%

See 1 more Smart Citation

CREB and AP‐1 activation regulates MKP‐1 induction by LPS or M‐CSF and their kinetics correlate with macrophage activation versus proliferation

et al. 2009

View full text Add to dashboard Cite

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 À380 and À180 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.Key words: Activation . Kinases . Macrophage . Phosphatases . Proliferation IntroductionMacrophages perform critical functions during the immune response. These cells are regulators of homeostasis and play an important role in innate and acquired immunity during infection, tumor growth, and wound healing [1]. In response to needs, tissue macrophages proliferate, further differentiate to more specialized macrophagic populations, or become activated. Macrophages, like many other cells of the immune system, are produced in large excess and most undergo apoptosis [2].In the presence of M-CSF, macrophages differentiate and proliferate. However, the proliferation of these cells is blocked when they are activated by Gram-negative LPS or by . Activation causes many biochemical, morphological and functional modifications. Macrophage response to M-CSF and LPS involves the phosphorylation of the three members of the MAPK family [4].MAPK are critical components of signal transduction pathways activated by a range of stimuli and they mediate a number of physiological and pathological changes in cell function [5,6]. MAPK activation requires phosphorylation on a threonine and tyrosine residue located in the activation loop. This process is reversible even in the continued presence of activating stimuli, thereby indicating that protein phosphatases regulate MAPK [7]. Although MAPK are conserved evolutionary pathways present in eukaryotic cells, the kinetics of activation and their subcellular compartmentalization are cell type-specific, and they orchestrate differential cellular responses. For example, in neuronal cells, sustained MAPK phosphorylation of even days is required for cellular activation or differentiation, while in fibroblasts, phosphorylation of this kinase family is very short. In contrast, to Immunol. 2009. 39: 1902-1913 Cristina Casals-Casas et al. 1902 achieve proliferation, extended activation of MAPK is required in these cells [6,7]. The correct spatio-temporal regulation of MAPK signalling is crucial in determining cellular responses to g...

show abstract

Section: Discussionmentioning

confidence: 79%

mentioning

confidence: 77%

CREB and AP‐1 activation regulates MKP‐1 induction by LPS or M‐CSF and their kinetics correlate with macrophage activation versus proliferation

et al. 2009

View full text Add to dashboard Cite

show abstract

“…Preferred targets are cJun N-terminal kinase (JNK) and p38 MAPK (Franklin and Kraft, 1997), although GC-induced expression of DUSP1 has also been linked to inhibition of the extracellular signal-regulated kinase (ERK) pathway in certain cell types (Kassel et al, 2001;Wu, Roth et al, 2006). The substrate selectivity of DUSP1 is not fully understood (Abraham and Clark, 2006).…”

Section: Dusp1mentioning

confidence: 99%

Anti-inflammatory functions of glucocorticoid-induced genes

Clark

2007

Molecular and Cellular Endocrinology

238

193

View full text Add to dashboard Cite

“…p38 mediates the free fatty acid-induced transcription of key gluconeogenic genes, including PEPCK (Collins et al, 2006). Furthermore, mice lacking MKP-1, which is a member of MAPK phosphatase and inactivates p38, are resistant to diet-induced obesity due to energy expenditure (Wu et al, 2006). ATF-2 was also suggested to regulate metabolism.…”

Section: Knockdown Flies As a Model Suitable For Study Of The Role Ofmentioning

confidence: 99%

ATF-2 Regulates Fat Metabolism inDrosophila

Okamura

Shimizu²,

Nagao³

et al. 2007

MBoC

View full text Add to dashboard Cite

ATF-2 is a member of the ATF/CREB family of transcription factors that is activated by stress-activated protein kinases such as p38. To analyze the physiological role of Drosophila ATF-2 (dATF-2), we generated dATF-2 knockdown flies using RNA interference. Reduced dATF-2 in the fat body, the fly equivalent of the mammalian liver and adipose tissue, decreased survival under starvation conditions. This was due to smaller triglyceride reserves of dATF-2 knockdown flies than control flies. Among multiple genes that control triglyceride levels, expression of the Drosophila PEPCK (dPEPCK) gene was strikingly reduced in dATF-2 knockdown flies. PEPCK is a key enzyme for both gluconeogenesis and glyceroneogenesis, which is a pathway required for triglyceride synthesis via glycerol-3-phosphate. Although the blood sugar level in dATF-2 knockdown flies was almost same as that in control flies, the activity of glyceroneogenesis was reduced in the fat bodies of dATF-2 knockdown flies. Thus, reduced glyceroneogenesis may at least partly contribute to decreased triglyceride stores in the dATF-2 knockdown flies. Furthermore we showed that dATF-2 positively regulated dPEPCK gene transcription via several CRE half-sites in the PEPCK promoter. Thus, dATF-2 is critical for regulation of fat metabolism.

show abstract

Mice lacking MAP kinase phosphatase-1 have enhanced MAP kinase activity and resistance to diet-induced obesity

Cited by 195 publications

References 52 publications

CREB and AP‐1 activation regulates MKP‐1 induction by LPS or M‐CSF and their kinetics correlate with macrophage activation versus proliferation

CREB and AP‐1 activation regulates MKP‐1 induction by LPS or M‐CSF and their kinetics correlate with macrophage activation versus proliferation

Anti-inflammatory functions of glucocorticoid-induced genes

ATF-2 Regulates Fat Metabolism inDrosophila

Contact Info

Product

Resources

About