Regulation of CREB Phosphorylation in the Suprachiasmatic Nucleus by Light and a Circadian Clock

Ginty, David D.; Kornhauser, Jon M.; Thompson, Margaret A.; Bading, Hilmar; Mayo, Kelly E.; Takahashi, Joseph S.; Greenberg, Michael E.

doi:10.1126/science.8097062

Cited by 786 publications

(536 citation statements)

References 25 publications

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“…Both kinds of stimuli induced the MKP-1 gene through the activation of the same transcription factors. While CREB is almost exclusively nuclear in both non-stimulated and stimulated cells [45,46], c-jun is an early gene induced by several stimuli. Because the kinetics of MKP-1 expression differed when macro- phages are induced to proliferate or to activate (Fig.…”

Section: The Early and Late Induction Of C-jun By Mcsf And Lps Correlmentioning

confidence: 99%

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

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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...

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Section: The Early and Late Induction Of C-jun By Mcsf And Lps Correlmentioning

confidence: 99%

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

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“…Using this approach, CREB, CREMa, ATF-1, Jun D and a Fos protein were identi®ed as proteins that interact with the CRE target sequence due to the ability of antibodies against these proteins to diminish the intensity of the DNA binding complex and to form a super-shifted band. The use of an antibody directed against the phosphorylated form of the ser 133 residue of CREB (Ginty et al, 1993) also detected the presence of phospho-ser 133 CREB in the CRE-DNA binding complex. In addition to Fos and Jun proteins, CREB and CREMa bound to the AP-1 target sequence, potentially accounting for the CRE DNA binding component of the AP-1 DNA binding complex.…”

Section: Activities Of Ap-1 and Cre Dna Binding Proteins In Keratinocmentioning

confidence: 99%

CRE DNA binding proteins bind to the AP-1 target sequence and suppress AP-1 transcriptional activity in mouse keratinocytes

et al. 1999

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Previously, we have shown that nuclear extracts from cultured mouse keratinocytes induced to di erentiate by increasing the levels of extra-cellular calcium contain Fra-1, Fra-2, Jun B, Jun D and c-Jun proteins that bind to the AP-1 DNA binding sequence. Despite this DNA binding activity, AP-1 reporter activity was suppressed in these cells. Here, we have detected the CREB family proteins CREB and CREMa as additional participants in the AP-1 DNA binding complex in di erentiating keratinocytes. AP-1 and CRE DNA binding activity correlated with the induction of CREB, CREMa and ATF-1 and CREB phosphorylation at ser 133 (ser 133 phospho-CREB) in the transition from basal to di erentiating keratinocytes, but the activity of a CRE reporter remained unchanged. In contrast, the CRE reporter was activated in the presence of the dominantnegative (DN) CREB mutants, KCREB and A-CREB, proteins that dimerize with CREB family members and block their ability to bind to DNA. The increase in CRE reporter activity in the presence of these mutants suggests that CRE-mediated transcriptional activity is suppressed in keratinocytes through protein-protein interactions involving a factor that dimerizes with the CREB leucine zipper. In experiments where the A-CREB mutant was co-transfected with an AP-1 reporter construct, transcriptional activity was also increased indicating that a CREB family member binds AP-1 sites and represses AP-1 transcriptional activity as well. Exogenous expression of the transcriptional repressor CREMa down-regulated both CRE and AP-1 reporters in keratinocytes suggesting that this factor may contribute to the suppression of AP-1 transcriptional activity observed in di erentiating keratinocytes.

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“…Aliquots of these extracts were analysed by Western blot as already reported (Monaco et al, 1995). As antibodies we used a polyclonal antibody recognizing the phosphorylated form of CREB at Ser-133 and CREMt at Ser-117 (Ginty et al, 1993; Upstate Biotechnology Incorporated, NY, USA); an ICER-speci®c polyclonal antibody raised against bacterially generated ICER ( Monaco et al, 1995); and an anti-CREB polyclonal antibody was used for determining equivalent protein loading (Upstate Biotechnology Incorporated, NY, USA).…”

Section: Protein Analysismentioning

confidence: 99%

Cross-talk in signal transduction: Ras-dependent induction of cAMP-responsive transcriptional repressor ICER by nerve growth factor

Monaco

Sassone–Corsi

1997

Oncogene

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The CREM gene encodes both activators and repressors of cAMP-induced transcription. By virtue of an alternative, intronic promoter within the gene, the ICER (Inducible cAMP Early Repressor) isoform is generated. ICER acts as a dominant negative regulator and is cAMP-inducible in various neuroendocrine cells and tissues. ICER negatively autoregulates its own expression, and appears to participate in the molecular events governing oscillatory hormonal regulations. Here we report that ICER is inducible with nerve growth factor (NGF). This is the ®rst example of cAMP-independent induction of ICER expression. Importantly, induction by NGF occurs via a subset of the CREs present in the ICER promoter which were previously shown to direct cAMP-inducibility. ICER induction correlates with a NGF-mediated phosphorylation of CREB. Both CREB phosphorylation and ICER inducibility require an intact Ras-dependent signalling pathway. We show that increased ICER levels result in the attenuation of c-fos expression. The activation of a powerful repressor of cAMP-responsive transcription by NGF, whose transduction signalling is cAMP-independent, constitutes a notable example of nuclear cross-talk and thus is likely to have relevant physiological implications.

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Regulation of CREB Phosphorylation in the Suprachiasmatic Nucleus by Light and a Circadian Clock

Cited by 786 publications

References 25 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

CRE DNA binding proteins bind to the AP-1 target sequence and suppress AP-1 transcriptional activity in mouse keratinocytes

Cross-talk in signal transduction: Ras-dependent induction of cAMP-responsive transcriptional repressor ICER by nerve growth factor

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