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At least 973 records · Page 54Linked to original sources
PubMed2003

Differential recruitment of the coactivator proteins CREB-binding protein and steroid receptor coactivator-1 to peroxisome proliferator-activated receptor gamma/9-cis-retinoic acid receptor heterodimers by ligands present in oxidized low-density lipoprotein.

Peroxisome proliferator-activated receptor gamma (PPARgamma) colocalizes with oxidized low-density lipoprotein (LDL) in foam cells in atherosclerotic lesions. We have explored a potential role of oxidized fatty acids in LDL as PPARgamma activators. LDL from patients suffering from intermittent claudication due to atherosclerosis was analyzed using HPLC and gas chromatography/mass spectrophotometry and found to contain 9-hydroxy and 13-hydroxyoctadecadienoic acid (9- and 13-HODE), as well as 5-hydroxy-, 12-hydroxy- and 15-hydroxyeicosatetraenoic acid (5-, 12- and 15-HETE respectively). PPARgamma was potently activated by 13(S)-HODE and 15(S)-HETE, as judged by transient transfection assays in macrophages or CV-1 cells. 5(S)- and 12(S)-HETE as well as 15-deoxy-Delta(12,14)-prostaglandin J(2) also activated PPARgamma but were less potent. Interestingly, the effect of the lipoxygenase products 13(S)-HODE and 15(S)-HETE as well as of the drug rosiglitazone were preferentially enhanced by the coactivator CREB-binding protein, whereas the effect of the cyclooxygenase product 15-deoxy-Delta(12,14)-prostaglandin J(2) was preferentially enhanced by steroid receptor coactivator-1. We interpret these results, which may have relevance to the pathogenesis of atherosclerosis, to indicate that the lipoxygenase products on the one hand and the cyclooxygenase product on the other exert specific effects on the transcription of target genes through differential coactivator recruitment by PPARgamma/9-cis retinoic acid receptor heterodimer complexes.

Aged↗
PubMed2002

Interaction between the hematopoietic Ets transcription factor Spi-B and the coactivator CREB-binding protein associated with negative cross-talk with c-Myb.

We have previously shown that the hematopoietic Ets transcription factor PU.1 interacts with the transcriptional coactivator CREB-binding protein (CBP). In this study, we further investigated whether Spi-B, another hematopoietic Ets transcription factor, also interacts with CBP. Direct physical interaction of Spi-B with CBP was demonstrated by glutathione S-transferase binding assay. Analysis using several deletion mutants of Spi-B and CBP revealed that the NH2-terminal region including the activation domain of Spi-B interacted with the region spanning amino acid residues 1283-1915 of CBP in vitro. The interaction of Spi-B with CBP was also observed in vivo. CBP potentiated Spi-B-mediated transcription of the reporter gene driven by the multimerized PU.1/Spi-B binding sites. This transcriptional activation by Spi-B and CBP was inhibited by expression of c-Myb, and the transcriptional activation by c-Myb and CBP was inhibited by expression of Spi-B, suggesting competition for CBP between these two transcription factors. Our results suggest that CBP acts as a transcriptional coactivator of Spi-B and mediates synergistic or antagonistic interactions between other transcription factors.

Acetyltransferases↗
PubMed2002

Retinoids and carnosol suppress cyclooxygenase-2 transcription by CREB-binding protein/p300-dependent and -independent mechanisms.

Treatment with retinoic acid (RA) or carnosol, two structurally unrelated compounds with anticancer properties, inhibited phorbol ester (PMA)-mediated induction of activator protein-1 (AP-1) activity and cyclooxygenase-2 (COX-2) expression in human mammary epithelial cells. The induction of COX-2 transcription by PMA was mediated by increased binding of AP-1 to the cyclic AMP response element (CRE) of the COX-2 promoter. Inhibition of the histone acetyltransferase activity of CREB- binding protein (CBP)/p300 blocked the induction of COX-2 by PMA. Treatment with carnosol but not RA blocked increased binding of AP-1 to the COX-2 promoter. Because AP-1 binding was unaffected by RA, we investigated whether RA inhibited COX-2 transcription via effects on the coactivator CBP/p300. Treatment with RA stimulated an interaction between RA receptor-alpha and CBP/p300; a corresponding decrease in the interaction between CBP/p300 and c-Jun was observed. Importantly, overexpressing CBP/p300 or dominant-negative RA receptor-alpha relieved the suppressive effect of RA on PMA-mediated stimulation of the COX-2 promoter. To elucidate the mechanism by which carnosol inhibited COX-2 transcription, its effects on protein kinase C (PKC) signaling were determined. Carnosol but not RA inhibited the activation of PKC, ERK1/2, p38, and c-Jun NH2-terminal kinase mitogen-activated protein kinase. Overexpressing c-Jun but not CBP/p300 reversed the suppressive effect of carnosol on PMA-mediated stimulation of COX-2 promoter activity. Thus, RA acted by a receptor-dependent mechanism to limit the amount of CBP/p300 that was available for AP-1-mediated induction of COX-2. By contrast, carnosol inhibited the induction of COX-2 by blocking PKC signaling and thereby the binding of AP-1 to the CRE of the COX-2 promoter. Taken together, these results show that small molecules can block the activation of COX-2 transcription by distinct mechanisms.

Abietanes↗
PubMed2006

Caffeine stimulates the proliferation of human lung adenocarcinoma cells and small airway epithelial cells via activation of PKA, CREB and ERK1/2.

The incidence of pulmonary adenocarcinoma (PAC) has increased dramatically over the last three decades. Recent studies have shown that human PAC cells with phenotypic features of bronchiolar Clara cells and experimentally induced PAC of Clara cell origin are under beta-adrenergic growth control. The phosphodiesterase inhibitor, theophylline, which is contained in tea, asthma/allergy medications and numerous dietary supplements selectively stimulated the growth of this cancer type in vivo and in vitro. The current study has tested the hypothesis that another environmentally prominent phosphodiesterase inhibitor, caffeine, has similar effects. Using a cell line derived from a human PAC with Clara cell features (PACC) and immortalized human small airway epithelial cells (SAECs), our data show that caffeine activated protein kinase A (PKA), the mitogen-activated kinases ERK1/2, the nuclear transcription factor cyclic AMP response element binding protein (CREB) and stimulated cell proliferation in these cell lines. These findings suggest that exposure to caffeine may contribute to the prevalence of PAC observed today.

Adenocarcinoma↗
PubMed2006

Growth stimulation of human pulmonary adenocarcinoma cells and small airway epithelial cells by beta-carotene via activation of cAMP, PKA, CREB and ERK1/2.

An alpha-tocopherol, beta-carotene supplementation trial (ATBC) and a chemoprevention trial with beta-carotene and retinoids (CARET trial) were conducted in the 1990s in populations at risk for the development of lung cancer. Both trials had to be discontinued due to significant increases in lung cancer and cardiovascular mortality. Clinical trials to test the cancer preventive effects of beta-carotene are still ongoing, and high concentrations of this provitamin are contained in numerous dietary supplements. Using a cell line derived from a human pulmonary adenocarcinoma (PAC) of Clara cell lineage and immortalized human small airway epithelial cells, our data show that low concentrations of beta-carotene that can be realistically expected in human tissues after oral administration caused a significant increase in intracellular cAMP and activated PKA, as well as in phosphorylation of ERK1/2 and CREB. Furthermore, the proliferation of cells was significantly stimulated by identical concentrations of beta-carotene as monitored by MTT assays. Control experiments with retinol also showed stimulation of cell proliferation and activation of PKA in both cell lines. In light of the fact that PAC is the leading type of lung cancer, these findings suggest that the growth promoting effects of beta-carotene on this cancer type observed in our experiments may have contributed to the unfortunate outcome of the ATBC and CARET trials. This interpretation is supported by the fact that elevated levels of cAMP in the cardiovascular system play a major role in the genesis of cardiovascular disease, which was also greatly promoted in the CARET trial. Our data challenge the widely accepted view that beta-carotene may be useful as a cancer preventive agent.

Adenocarcinoma↗
PubMed2006

Myotube depolarization generates reactive oxygen species through NAD(P)H oxidase; ROS-elicited Ca2+ stimulates ERK, CREB, early genes.

Controlled generation of reactive oxygen species (ROS) may contribute to physiological intracellular signaling events. We determined ROS generation in primary cultures of rat skeletal muscle after field stimulation (400 1-ms pulses at a frequency of 45 Hz) or after depolarization with 65 mM K+ for 1 min. Both protocols induced a long lasting increase in dichlorofluorescein fluorescence used as ROS indicator. Addition of diphenyleneiodonium (DPI), an inhibitor of NAD(P)H oxidase, PEG-catalase, a ROS scavenger, or nifedipine, an inhibitor of the skeletal muscle voltage sensor, significantly reduced this increase. Myotubes contained both the p47phox and gp91phox phagocytic NAD(P)H oxidase subunits, as revealed by immunodetection. To study the effects of ROS, myotubes were exposed to hydrogen peroxide (H2O2) at concentrations (100-200 microM) that did not alter cell viability; H2O2 induced a transient intracellular Ca2+ rise, measured as fluo-3 fluorescence. Minutes after Ca2+ signal initiation, an increase in ERK1/2 and CREB phosphorylation and of mRNA for the early genes c-fos and c-jun was detected. Inhibition of ryanodine receptor (RyR) decreased all effects induced by H2O2 and NAD(P)H oxidase inhibitors DPI and apocynin decreased ryanodine-sensitive calcium signals. Activity-dependent ROS generation is likely to be involved in regulation of calcium-controlled intracellular signaling pathways in muscle cells.

Animals↗
PubMed2004

Implications of transcriptional coactivator CREB binding protein complexes in rheumatoid arthritis.

Transcriptional coactivators have crucial roles in eukaryotic transcription. It has been suggested that one of the coactivators, cAMP response element binding protein (CREB) binding protein (CBP), regulates gene expression with a number of transcription factors via two mechanisms. One is the recruitment of general transcriptional machinery to the promoters. The other is its intrinsic and associated histone acetyltransferase (HAT) activity, which increases the accessibility of the activator to DNA, and the acetylation of nonhistone proteins. Rheumatoid arthritis (RA) is characterized by the inflammation and proliferation of synovium, leading to the destruction of articular cartilage and bone. To understand the pathogenesis of RA, we focused the transcription mechanism through CBP in synoviocytes and chondrocytes. We identified Notch-1 in synoviocytes and p34(SEI-1) in chondrocytes as CBP binding proteins by yeast two-hybrid screening. It was also suggested that the acetylation of p53 could repress transactivation in RA synoviocytes. These associations may regulate proliferation and apoptosis. This study suggests that regulation of the coactivator could become a novel strategy for RA therapy.

Journal Article↗
PubMed2006

Transcriptional dysregulation in Down syndrome: predictions for altered protein complex stoichiometries and post-translational modifications, and consequences for learning/behavior genes ELK, CREB, and the estrogen and glucocorticoid receptors.

The phenotype of Down syndrome, trisomy of chromosome 21, is hypothesized to be produced by the increased expression due to gene dosage of normal chromosome 21 genes. Chromosome 21 encodes a number of proteins that, based on experimental evidence or domain composition, are classed as transcription factors or their co-regulators. Other chromosome 21 proteins contribute to post-translational modification of transcription factors, including their phosphorylation, dephosphorylation and sumoylation. Several of these chromosome 21 proteins and the pathways in which they function have overlapping transcription factor specificities. Thus, altered stoichiometry in complexes and altered levels of activation of individual transcription factors may contribute to the Down syndrome phenotype by perturbation of downstream gene expression. Here we review recent data on four chromosome 21 proteins: NRIP1, GABPA, DYRK1A and SUMO3. We discuss the implications for activation of ELK, CREB, C/EBP alpha, beta estrogen and glucocorticoid receptors, and for expression of BDNF. Each of these proteins is relevant to learning, behavior and/or development and therefore perturbation of their activation may contribute to the Down syndrome phenotype.

Chromosome Mapping↗
PubMed2005

Increased expression of interleukin-6 by vasoactive intestinal peptide is associated with regulation of CREB, AP-1 and C/EBP, but not NF-kappaB, in mouse calvarial osteoblasts.

Interleukin-6 (IL-6), and the related cytokines IL-11, leukemia inhibitory factor (LIF) and oncostatin M (OSM), are potent stimulators of osteoclastic bone resorption. In the present study, we have addressed the possibility that the neuropeptide vasoactive intestinal peptide (VIP) may regulate the production of and/or sensitivity to the IL-6 family of cytokines in mouse calvarial osteoblasts. VIP stimulated IL-6 mRNA expression and protein release in a time- and concentration-dependent manner, whereas mRNA expression of the IL-6 receptor, as well as mRNA expressions of IL-11, LIF, OSM and their cognate receptors, were unaffected by VIP. In cells transfected with the IL-6 promoter coupled to luciferase, VIP increased transcriptional activity. The effects of VIP were shared by the related neuropeptide PACAP-38, belonging to the same superfamily of neuropeptides, whereas secretin did not have any effect, indicating that the effects were mediated by VPAC2 receptors. The effects of VIP were potentiated by the cyclic AMP phosphodiesterase inhibitor rolipram and mimicked by forskolin, indicating the involvement of the cyclic AMP/protein kinase A pathway. This was further demonstrated by the facts that the stimulatory effect of VIP on luciferase activity could be reversed by the PKA inhibitors H-89 and KT5720 and was mimicked by cyclic AMP analogues selective for PKA, but not by those selective for Epac. In addition, VIP enhanced the phosphorylation of CREB, as assessed by both immunocytochemical analysis and Western blot. The DNA binding activity of nuclear extracts to C/EBP was increased by VIP, whereas binding to AP-1 was decreased. In contrast, DNA binding to NF-kappaB, as well as nuclear translocation of NF-kappaB and C/EBP, were unaffected by VIP. The mRNA expressions of C/EBPbeta, C/EBPdelta, C/EBPgamma, c-Jun, JunB, c-Fos, Fra-1 and IkappaBalpha and protein level of IkappaBalpha were all unaffected by VIP. These observations, together, demonstrate that VIP stimulates IL-6 production in osteoblasts by a mechanism likely to be mediated by VPAC2 receptors and dependent on cyclic AMP/protein kinase A/CREB activation and also involving the transcription factors C/EBP and AP-1.

3T3 Cells↗
PubMed2006

Curcumin reverses the effects of chronic stress on behavior, the HPA axis, BDNF expression and phosphorylation of CREB.

Curcuma longa is a major constituent of the traditional Chinese medicine Xiaoyao-san, which has been used to effectively manage stress and depression-related disorders in China. Curcumin is the active component of curcuma longa, and its antidepressant effects were described in our prior studies in mouse models of behavioral despair. We hypothesized that curcumin may also alleviate stress-induced depressive-like behaviors and hypothalamic-pituitary-adrenal (HPA) axis dysfunction. Thus in present study we assessed whether curcumin treatment (2.5, 5 and 10 mg/kg, p.o.) affects behavior in a chronic unpredictable stress model of depression in rats and examined what its molecular targets may be. We found that subjecting animals to the chronic stress protocol for 20days resulted in performance deficits in the shuttle-box task and several physiological effects, such as an abnormal adrenal gland weight to body weight (AG/B) ratio and increased thickness of the adrenal cortex as well as elevated serum corticosterone levels and reduced glucocorticoid receptor (GR) mRNA expression. These changes were reversed by chronic curcumin administration (5 or 10 mg/kg, p.o.). In addition, we also found that the chronic stress procedure induced a down-regulation of brain-derived neurotrophic factor (BDNF) protein levels and reduced the ratio of phosphorylated cAMP response element-binding protein (pCREB) to CREB levels (pCREB/CREB) in the hippocampus and frontal cortex of stressed rats. Furthermore, these stress-induced decreases in BDNF and pCREB/CREB were also blocked by chronic curcumin administration (5 or 10 mg/kg, p.o.). These results provide compelling evidence that the behavioral effects of curcumin in chronically stressed animals, and by extension humans, may be related to their modulating effects on the HPA axis and neurotrophin factor expressions.

Adrenal Glands↗
PubMed2005

Inhibitory effects of the extracts of Sutherlandia frutescens (L.) R. Br. and Harpagophytum procumbens DC. on phorbol ester-induced COX-2 expression in mouse skin: AP-1 and CREB as potential upstream targets.

Numerous anti-inflammatory agents have been shown to exert chemopreventive activity by targeting cyclooxygenase (COX)-2, a rate-limiting enzyme involved in the inflammatory process. Sutherlandia frutescens (L.) R. Br. and Harpagophytum procumbens DC., which are commonly known as Cancer bush (CB) and Devil's claw (DC), respectively, have long been used in South Africa for the management of pain and inflammation. In the present study, we investigated the effects of methanolic extracts of CB and DC on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced COX-2 expression in mouse skin. Topical application of both extracts inhibited TPA-induced COX-2 expression. As an underlying mechanism of COX-2 inhibition, these extracts diminished TPA-stimulated catalytic activity of extracellular signal-regulated protein kinase (ERK), which is known to regulate the activation of eukaryotic transcription factors mediating COX-2 induction. While TPA-induced activation of nuclear factor-(kappa)B remained unaffected by both extracts, they inhibited TPA-induced activation of activator protein-1 (AP-1) and attenuated the expression of its key component c-Fos. In another study, topical application of TPA induced DNA binding of cyclic AMP response element binding (CREB) protein in mouse skin in vivo, which was abrogated by pretreatment with either CB or DC.

Administration, Topical↗
PubMed2006

Expression of the human TPT1 gene coding for translationally controlled tumor protein (TCTP) is regulated by CREB transcription factors.

Re-evaluation of genomic and cDNA data revealed that the human TPT1 gene coding for the translationally controlled tumor protein (TCTP) consists of at least 4211 base pairs. It is transcribed into two transcripts of about 0.8 and 1.2 kb, which contain the same coding region and 5'-UTR, but differ in the length of 3'-UTRs by the use of alternative polyadenylation signals. 459 bp promoter sequences were analyzed by theoretical evaluation, reporter-gene assays, gelshift and footprinting experiments to search for transcription factor binding sites. The promoter contains two highly conserved CRE sites between -50 and -89 in close vicinity to a TATA-box at -30. Supershift assays identified CREB I and Fra II of the CREB/ATF1/AP1 family as factors interacting with the CRE/AP1 site. A 3-5-fold stimulation of TCTP synthesis by forskolin and phorbolester in T24 cells and promoter-reporter experiments using CRE-deletion constructs suggested a transcriptional control by cAMP signaling via phosphorylation dependent activation of CRE/CREB interaction.

5' Flanking Region↗
PubMed2005

Purinergic receptor modulation of BV-2 microglial cell activity: potential involvement of p38 MAP kinase and CREB.

ATP is abundant in the extracellular fluid following brain injury, and it exerts potent modulatory effects on microglia, whose hyperactivation is thought to exacerbate neuronal damage. We show here that ATP decreases LPS-stimulated iNOS and COX-2 expression and reduces NO release in BV-2 microglia by a mechanism involving p38 MAP kinase. Further, we demonstrate that the inhibitory effects of ATP on NO production occur within 30 min of exposure and correlate with activation of the transcription factor CREB. Together, these data suggest that ATP may exert neuroprotective effects in the brain via a mechanism involving augmented activation of the p38/CREB pathway.

Adenine Nucleotides↗
PubMed1998

Cell cycle regulation of the transcriptional coactivators p300 and CREB binding protein.

To respond to changes in its environment, the cell utilizes mechanisms that integrate extracellular signals with specific changes in gene expression. To better understand these critical regulatory mechanisms, research has focused, for the most part, on the identification of sequence-specific DNA-binding proteins, such as the nuclear factor kappaB (NF-kappaB) or activator protein 1 (AP-1) families of transcription factors, that interact with the promoter and enhancer elements of genes induced or repressed during cellular activation. More recently, however, it has become apparent that non-DNA-binding transcriptional coactivators, such as p300 and CREB binding protein (CBP), previously thought to function primarily as "bridging" proteins between DNA-bound transcription factors and the basal transcription complex, play a critical regulatory role as integrators of diverse signalling pathways with the selective induction of gene expression. In this commentary, we shall discuss the implications of a particular aspect of this growing and expanding field: how cell cycle regulation of p300 and CBP impacts our understanding of cellular differentiation, the response to DNA damage, and oncogenesis.

Cell Cycle↗
PubMed1997

Enhanced CREB phosphorylation and changes in c-Fos and FRA expression in striatum accompany amphetamine sensitization.

Expression in striatum of c-Fos, a 35 kDa Fos-related antigen (FRA) and the phosphorylated form of cyclic AMP response element binding protein (phosphoCREB) was assessed using Western blots in rats that developed behavioral sensitization following repeated amphetamine administration. Treatment with d-amphetamine (5 mg/kg) for 5 consecutive days produced behavioral sensitization. Similar to previous observations using chronic cocaine administration, amphetamine sensitized animals had decreased c-Fos and increased FRA proteins in striatum. Supershift analysis with antisera to c-Fos and FRA proteins demonstrated that 4-Fos and the 35 kDa FRA are components of the striatal AP-1 binding complex from sensitized rats. Thus, amphetamine sensitization is accompanied by alterations in the composition of the AP-1 DNA binding complex. An increased amount of phosphoCREB protein was also present in the striatum of amphetamine sensitized rats. These results suggest that alterations in Fos, FRA and CREB transcription factors are common neuronal responses to chronic psychostimulant administration and may contribute to regulation of genes important to the neuroplastic changes underlying psychostimulant sensitization.

Activating Transcription Factor 2↗
PubMed1998

Conformational preferences in the Ser133-phosphorylated and non-phosphorylated forms of the kinase inducible transactivation domain of CREB.

Phosphorylation of Ser133 within the kinase inducible transactivation domain (KID) of the transcription factor CREB potentiates interaction with the KIX domain of coactivator CBP. Heteronuclear NMR spectroscopic analyses reveal that the KID domain is largely unstructured except for residues that comprise the alphaA helix in the pKID-KIX complex, which populate helical conformations to a significant extent (>50%). The helical content in the alphaB region is very small in the non-phosphorylated form (approximately 10%) although a small increase is detected upon Ser133 phosphorylation. The intrinsic bias towards helical conformations probably facilitates folding of the KID domain upon binding to KIX while the principal role of the phosphate group appears to be largely in mediating the intermolecular interactions in the pKID-KIX complex.

Amino Acid Sequence↗
PubMed1997

Design of a multiple slice interface chamber and application for resolving the temporal pattern of CREB phosphorylation in hippocampal long-term potentiation.

We describe an improved method for the investigation of time-dependent intracellular events giving rise to long-lasting changes in synaptic efficacy. A new interface chamber for the simultaneous superfusion of approximately 30 rat hippocampal slices was designed. The slice chamber contains an upper and a lower medium reservoir connected by a grooved incubation platform which is mounted at an angle of 7 degrees on a thermoregulation unit. Surface slices placed in the chamber are perfused with oxygenated medium at a rate of 1 ml/min and are maintained synaptically viable for at least 6 h. At different time points after induction of long-term potentiation by stimulation of the Schaffer collateral pathway, slices were either fixed in Zamboni's fixative or the CA1 region was excised and lysed in boiling SDS-sample buffer. Fixed 400 microm hippocampal slices were cut into 30 microm sections and immunocytochemically stained with an anti-serine 133 phosphorylated cAMP-responsive element binding protein (pCREB) antibody. Binding of primary antibody was detected with the avidin-biotinylated peroxidase complex method and enhanced using peroxidase-catalyzed deposition of biotinylated tyramine. Staining was visualized with streptavidin-cyanine 3.18 and observed under a confocal laser scanning microscope. CA1 lysates were electrophoresed and subjected to Western blot analysis. Both pCREB immunocytochemical staining and Western blotting showed that CREB is rapidly and transiently phosphorylated after induction of long-term potentiation. pCREB levels peaked within 30 min and declined back to control after 60 min. Immunocytochemistry also showed that pCREB was localized to the nuclei of CA1 pyramidal cells near the tetanization site.

Animals↗
PubMed1998

CREB-induced transcriptional activation depends on mGluR6 in rod bipolar cells.

To investigate the molecular mechanisms of stimuli-induced transcriptional activation in neuronal cells, we have investigated the light-induced gene expression in the neural retina of rats. The immunoreactivity for phosphorylated cAMP responsive element binding protein (PCREB-IR) was expressed in the outer half of the inner nuclear layer (INL) and the ganglion cell layer (GCL) after 5 min exposure to steady light also in mice. In addition to these cells, PCREB-IR was also detected in the inner border of the INL after 5 min exposure to flashing light. Both steady and flashing lights induced c-fos mRNA in the same types of cells as the PCREB-IR-positive cells. Majority of PCREB immunoreactive nuclei in the outer half of the INL were also immunopositive for anti-protein kinase C alpha (PKC alpha), a marker of rod bipolar cells, while CaM kinase IV immunoreactivity was not detected in these cells. PCREB-IR and c-fos gene expression in the PKC alpha positive rod bipolar cells were lost in mice lacking metabotropic glutamate receptor 6 (mGluR6). Thus, we propose that the transcriptional response of CREB to light stimulation in rod bipolar cells is regulated via mGluR6.

Animals↗