Abstract:
:The duration of ERK1/2 activation influences the nature of the biological response to agonist. Members of the AP-1 transcription factor family are well known targets of the ERK1/2 pathway and are expressed in a temporally coordinated fashion during cell cycle re-entry. In CCl39 fibroblasts, sustained ERK1/2 activation is required for the expression of Fra-1, Fra-2, c-Jun and JunB, whereas expression of c-Fos is still strongly induced even in response to transient ERK activation. However, the significance of this pattern of expression for AP-1 activity has not been addressed. Here we show that growth factor stimulated activation of the C-terminal c-Fos transactivation domain (TAD) serves as a sensor for ERK1/2 signal duration whereas the c-JunTAD is not responsive to growth factors. In addition, sustained ERK1/2 activation determines the duration of increases in AP-1 DNA binding complexes as well as their qualitative make up. Finally, this is reflected in both the duration and quantitative transcriptional output of stably integrated AP-1 reporter constructs, indicating that AP-1 activity is finely tuned to ERK1/2 signal duration. These results provide new insights into the importance of ERK1/2 signal duration in the regulation of AP-1 and provide an explanation for how differences in signal duration can lead to both quantitative and qualitative changes in gene expression.
journal_name
Cell Signaljournal_title
Cellular signallingauthors
Chalmers CJ,Gilley R,March HN,Balmanno K,Cook SJdoi
10.1016/j.cellsig.2006.09.001subject
Has Abstractpub_date
2007-04-01 00:00:00pages
695-704issue
4eissn
0898-6568issn
1873-3913pii
S0898-6568(06)00212-9journal_volume
19pub_type
杂志文章abstract::Since its discovery in biopsies from breast cancer patients, the effect of corticotropin-releasing hormone (CRH) on carcinoma progression is still unclear. Transforming growth factorβ1 (TGFβ1) promotes Epithelial-Mesenchymal Transition (EMT) and induces Snail1 and Twist1 expressions. Loss of epithelial cadherin (E-cad...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2013.12.017
更新日期:2014-04-01 00:00:00
abstract::The ubiquitously expressed phosphoinositide 3-kinase (PI3K) family of lipid kinases control diverse cellular functions including cell survival, proliferation, metabolism and migration. Class I PI3Ks generate two distinct 3-phosphoinositide lipid messengers, PI(3,4,5)P3 (PIP3) and PI(3,4)P2, that recruit signaling effe...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2015.05.013
更新日期:2015-09-01 00:00:00
abstract::15-lipoxygenase (15-LO) is known to play an important role in chronic pulmonary hypertension. Accumulating evidence for its down-stream participants in the vasoconstriction and remodeling processes of pulmonary arteries, while how hypoxia regulates 15-LO/15-hydroxyeicosatetraenoic acid (15-HETE) to mediate hypoxic pul...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2012.06.007
更新日期:2012-10-01 00:00:00
abstract::Deficits in brain function that are associated with aging and age-related diseases benefit very little from currently available therapies, suggesting a better understanding of the underlying molecular mechanisms is needed to develop improved drugs. Here, we review the literature to test the hypothesis that a break dow...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2017.11.004
更新日期:2018-01-01 00:00:00
abstract::We report on a novel method to monitor changes in intracellular cAMP concentration ([cAMP]i) within intact living cells using a chimeric fusion of the catalytic subunit of cAMP-dependent protein kinase to green fluorescent protein (PKAcat-GFP). In stably transfected unstimulated fibroblasts, fusion protein fluorescenc...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2004.01.006
更新日期:2004-08-01 00:00:00
abstract::In more than 90% of cancers including glioma, telomere elongation reverse transcriptase (hTERT) is overexpressed. In the present study, we sought to explore whether matrix metalloproteinase-9 (MMP-9) shRNA could alter hTERT-mediated proliferation in glioma cells. MMP-9 shRNA induced senescence and apoptosis in glioma ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2011.08.001
更新日期:2011-12-01 00:00:00
abstract::PRK1/PKN is a member of the protein kinase C (PKC) superfamily of serine/threonine protein kinases. Despite its important role as a RhoA effector, limited information is available regarding how this kinase is regulated. We show here that the last seven amino acid residues at the C-terminus is dispensable for the catal...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2004.12.003
更新日期:2005-09-01 00:00:00
abstract::CC chemokine receptor 5 (CCR5) is a seven-transmembrane, G protein-coupled receptor (GPCR) which regulates trafficking and effector functions of memory/effector T-lymphocytes, macrophages, and immature dendritic cells. It also serves as the main coreceptor for the entry of R5 strains of human immunodeficiency virus (H...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2004.04.007
更新日期:2004-11-01 00:00:00
abstract::We demonstrated previously an inhibitory effect of luminal leptin on glucose absorption in differentiated Caco-2 cells. Since this process is dependent on the Na(+) gradient established by the Na(+)/K(+)ATPase this work was undertaken to investigate if the ATPase is one of the hormone's targets. Fully differentiated C...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2014.12.004
更新日期:2015-03-01 00:00:00
abstract::GRB2 related adaptor protein downstream of Shc (GADS) is a member of the GRB2 family of adaptors and is critical for TCR-induced signaling. The current model is that GADS recruits SLP-76 to the LAT complex, which facilitates the phosphorylation of SLP-76, the activation of PLC-γ1, T cell adhesion and cytokine producti...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2015.01.012
更新日期:2015-04-01 00:00:00
abstract::The present study was undertaken to investigate whether purified ras proteins can affect the activity of polyphosphoinositide specific phospholipase C in a cell-free membrane system. For this purpose we used homogenous preparations of the proto-oncogenic (H-ras(gly 12)) and the oncogenic (H-ras(val 12)) forms of the h...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/0898-6568(90)90050-k
更新日期:1990-01-01 00:00:00
abstract::Recent studies have shown DAPk as a molecular modulator induced by the second messenger, responsible for controlling cell destiny decisions, but the detailed mechanism mediating the role of DAPk1 during cell death is still not fully understood. In this present report, we attempted to characterize the effects of TNF-α ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2012.03.010
更新日期:2012-07-01 00:00:00
abstract::Understanding the underlying mechanism by which cancer cells acquire resistance to radiation and favorably selected for its clonal expansion will provide molecular insight into tumor recurrence at the treatment site. In the present study, we investigated the molecular mechanisms prompted in MCF-7 breast cancer cells i...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2017.01.011
更新日期:2017-02-01 00:00:00
abstract::Interferon-α (IFNα) has enormous potential for anti-proliferative and anti-viral treatments. However, clinical success is still hampered due to its limited bioavailability and thus, lack of sustained modulation of disease-relevant protective programs. Consequently, we here examined whether IFNα immobilized on nanoscal...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2013.01.012
更新日期:2013-04-01 00:00:00
abstract::The inwardly rectifying K+ channels of the GIRK (Kir3) family, members of the superfamily of inwardly rectifying K+ channels (Kir), are important physiological tools to regulate excitability in heart and brain by neurotransmitters, and the only ion channels conclusively shown to be activated by a direct interaction wi...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/s0898-6568(97)00095-8
更新日期:1997-12-01 00:00:00
abstract::Staphylococcal alpha-toxin at subcytotoxic concentrations stimulated phosphatidylinositol turnover and arachidonic acid release in undifferentiated cultures of pheochromocytoma PC12 cells. Stimulation of phospholipase A2 but not C was dependent on extracellular calcium. Addition of staphylococcal alpha-toxin to PC12 c...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/0898-6568(89)90057-0
更新日期:1989-01-01 00:00:00
abstract::The effects of estrogen in breast epithelial cells are mediated primarily via estrogen receptor alpha and estrogen receptor beta (ERalpha and ERbeta). Accumulating evidence implicates a role for Ca2+ and calmodulin in breast carcinoma, as well as in the function of ERalpha. Calmodulin contributes to the regulation of ...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2006.08.018
更新日期:2007-03-01 00:00:00
abstract::Calcium/calmodulin dependent protein kinase IIδ (CaMKIIδ) acts as a molecular switch regulating cardiovascular Ca2+ handling and contractility in health and disease. Activation of CaMKIIδ is also known to regulate cardiovascular inflammation and is reported to be required for pro-inflammatory NF-κB signalling. In this...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2018.07.008
更新日期:2018-11-01 00:00:00
abstract::Eight paralogue members form the family of transmembrane channel-like (TMC) proteins that share considerable sequence homology to anoctamin 1 (Ano1, TMEM16A). Ano1 is a Ca(2+) activated Cl(-) channel that is related to head and neck cancer, often caused by human papilloma virus (HPV) infection. Mutations in TMC 6 and ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2014.09.001
更新日期:2014-12-01 00:00:00
abstract::Interleukin-2 (IL-2) is the major growth factor of activated T lymphocytes. By inducing cell cycle progression and protection from apoptosis in these cells, IL-2 is involved in the successful execution of an immune response. Upon binding its receptor, IL-2 activates a variety of signal transduction pathways, including...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/s0898-6568(03)00003-2
更新日期:2003-06-01 00:00:00
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2012.02.001
更新日期:2012-06-01 00:00:00
abstract::As a member of the Rab small GTPase family, Rab11a has been shown to be involved in different vesicle trafficking processes. In earlier work we identified Rab11a to be present in GLUT4-containing vesicles after insulin stimulation and showed its involvement in insulin-dependent glucose uptake. However, it remained elu...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2006.10.008
更新日期:2007-04-01 00:00:00
abstract::Heat shock protein 90 (Hsp90) serves to stabilise and correctly fold multiple significant client proteins associated with cell proliferation and cell survival. However, little is known about the Hsp90 client proteins that regulate cell metabolism. Here, we describe a unique ability of Hsp90 to regulate the stability a...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2011.12.001
更新日期:2012-04-01 00:00:00
abstract::A critical aspect of understanding the regulation of signal transduction is not only to identify the protein-protein interactions that govern assembly of signaling pathways, but also to understand how those pathways are regulated in time and space. In this report, we have applied both gain-of-function and loss-of-func...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2018.06.006
更新日期:2018-10-01 00:00:00
abstract::We have studied modulation of "store-operated calcium influx" by tyrosine phosphatases in the pancreatic acinar cell line AR42J and in HEK 293 cells. We show that inhibition of tyrosine phosphatases by bis-(N,N-dimethyl-hydroxamido) hydrooxovanadate (DMHV) leads to an increase in Ca(2+) release-activated Ca(2+) (CRAC)...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/s0898-6568(03)00088-3
更新日期:2003-12-01 00:00:00
abstract::Peroxisome proliferator-activated receptor γ (PPARγ) is a member of the nuclear receptor family and plays key roles in glucose and lipid metabolism. Its transcriptional control of target genes is mediated by ligand-dependent recruitment of coactivators. In this study, we demonstrate that a novel transcriptional modula...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2014.11.035
更新日期:2015-03-01 00:00:00
abstract::Neuroprotective effects of alpha(2)-adrenergic receptor (AR) agonists are mediated via the alpha(2A)AR subtype, but the molecular mechanisms underlying these actions are still not elucidated. A two-hybrid screen was performed to identify new proteins that may control alpha(2)AR receptor function and trafficking. This ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2009.05.011
更新日期:2009-10-01 00:00:00
abstract::Skeletal muscle is highly adapted to respond to oxidative imbalances, since it is continuously subjected to an increased production of reactive oxygen species (ROS) during exercise. Oxidative stress, however, has been associated with skeletal muscle atrophy and damage in many diseases. In this study, we examined wheth...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2006.05.004
更新日期:2006-12-01 00:00:00
abstract::DMSO differentiated U937 cells responded to 10(-6) M LTD4, LTB4 and FMLP with an increase in both InsP formation and [Ca2+]i. FMLP caused a greater rise in InsPs than either LTD4 or LTB4, which were equivalent. LTD4, however, caused a greater increase in [Ca2+]i than LTB4 (4-fold) or FMLP. The FMLP [Ca2+]i and InsP re...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/0898-6568(90)90078-o
更新日期:1990-01-01 00:00:00
abstract::Previous studies from acutely transfected HeLa cells have identified an acidic alpha-helix in the Type IIbeta PtdIns5P 4-kinase (PIPkin IIbeta) as a putative novel nuclear localisation sequence (Ciruela et al. Biochem. J. 364, 587-591 2000). However, some heterogeneity in cellular localisation was always observed, and...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2007.01.010
更新日期:2007-06-01 00:00:00