Abstract：
:Platelet-activating factor (PAF) is a potent phospholipid mediator involved in several diseases such as allergic asthma, atherosclerosis and psoriasis. The human PAF receptor (PAFR) is a member of the G-protein-coupled receptor family. Following stimulation, PAFR becomes rapidly desensitized; this refractory state is dependent on PAFR phosphorylation, internalization and down-regulation. In this report, we show that the PAFR inverse agonist, WEB2086, can induce phosphorylation and down-regulation of PAFR. Using selective inhibitors, we determined that the agonist, PAF, and WEB2086 could induce phosphorylation of PAFR by PKC. Moreover, dominant-negative (DN) mutant of PKC isoforms beta inhibited WEB2086-stimulated PAFR phosphorylation, whereas PAF-stimulated phosphorylation was inhibited by DN PKCalpha and delta. WEB2086 also induced PAFR down-regulation which could be blocked by PKC inhibitors and by DN PKCbeta. WEB2086-induced down-regulation was dynamin-dependent but arrestin-independent. Unlike PAF, WEB2086-stimulated intracellular trafficking of PAFR was independent of Rab5. Specific inhibitors of lysosomal proteases and of proteasomes were both effective in reducing WEB2086-induced PAFR down-regulation, indicating the importance of receptor targeting to both lysosomes and proteasomes in long-term cell desensitization to WEB2086. These results indicate that although both agonists and inverse agonists induce receptor PAFR down-regulation, this may be accomplished through different signal transduction and trafficking pathways.
journal_name
Cell Signaljournal_title
Cellular signallingauthors
Dupré DJ,Thompson C,Chen Z,Rollin S,Larrivée JF,Le Gouill C,Rola-Pleszczynski M,Stanková Jdoi
10.1016/j.cellsig.2007.05.015subject
Has Abstractpub_date
2007-10-01 00:00:00pages
2068-79issue
10eissn
0898-6568issn
1873-3913pii
S0898-6568(07)00158-1journal_volume
19pub_type
杂志文章abstract：:Ketone bodies β-hydroxybutyrate (BHB) and acetoacetate are important metabolic substrates for energy production during prolonged fasting. However, BHB also has signaling functions. Through several metabolic pathways or processes, BHB modulates nutrient utilization and energy expenditure. These findings suggest that BH...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
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更新日期：2016-08-01 00:00:00
abstract：:Expression of the human cytomegalovirus (HCMV)-encoded chemokine receptor homologue pUS28 in mammalian cells results in ligand-dependent and -independent changes in the activity of multiple cellular signal transduction pathways. The ligand-dependent signalling activity of pUS28 has been shown to be predominantly media...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2008.04.010
更新日期：2008-08-01 00:00:00
abstract：:Long-term amino acid starvation represents a form of metabolic stress which stimulates gene expression. Here we report that depriving HeLa cells for any one of a series of amino acids activates c-Jun N-terminal kinase-1 (JNK-1). In contrast, the other mitogen-activated protein kinases (MAPKs) ERK-1 and, to a lesser ex...
journal_title：Cellular signalling
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journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2017.01.026
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journal_title：Cellular signalling
pub_type： 杂志文章,评审
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更新日期：2000-10-01 00:00:00
abstract：BACKGROUND:MicroRNAs (miRNAs) are key regulators of many cellular pathways. However, the picture for components or regulators involved in the process of miRNA biogenesis and function remains to be further elucidated. Early growth response gene 1 (Egr1) has long been considered as tumor suppressor and transcriptional fa...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2015.02.016
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journal_title：Cellular signalling
pub_type： 杂志文章
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更新日期：2019-01-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2009.05.004
更新日期：2009-10-01 00:00:00
abstract：:The mammalian target of rapamycin complex 1(mTORC1) integrates diverse signals to control cell growth, proliferation, survival, and metabolism. Role of reactive oxygen species (ROS) on mTORC1 signaling remains obscure and mechanisms through which ROS modulate mTORC1 are not known.We demonstrate that low doses ROS expo...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2010.05.015
更新日期：2010-10-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
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更新日期：2015-12-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2005.04.003
更新日期：2005-09-01 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：10.1016/0898-6568(95)00019-l
更新日期：1995-07-01 00:00:00
abstract：:Nuclear receptors (NRs) orchestrate the transcription of specific gene networks in response to binding of their cognate ligand. They also act as mediators in a variety of signalling pathways through integrating diverse phosphorylation events. NR phosphorylation concerns all three major domains, the N-terminal activati...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/s0898-6568(02)00115-8
更新日期：2003-04-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2019.109420
更新日期：2019-12-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2014.04.021
更新日期：2014-09-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2008.07.008
更新日期：2008-11-01 00:00:00
abstract：:Microglia play a prominent role in the brain's inflammatory response to injury or infection by migrating to affected locations, secreting inflammatory molecules, and phagocytosing damaged tissue. However, because severe or chronic neuroinflammation exacerbates many neurological conditions, controlling microglia action...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2008.10.014
更新日期：2009-02-01 00:00:00
abstract：:Mice lacking the gene for suppressor of cytokine signaling 1 (SOCS1) show defective homeostasis of T lymphocytes due to accumulation of CD8(+) T cells, resulting at least partly from dysregulated IL-15 signaling. IL-15 alone does not stimulate proliferation of naïve CD8 T cells, but can synergize with IL-21 to induce ...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2006.10.003
更新日期：2007-04-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/s0898-6568(01)00268-6
更新日期：2002-04-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
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更新日期：2020-12-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2014.05.010
更新日期：2014-09-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2012.09.027
更新日期：2013-01-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/0898-6568(95)02034-9
更新日期：1996-02-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/s0898-6568(98)00052-7
更新日期：1999-03-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2013.11.007
更新日期：2014-02-01 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
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/s0898-6568(97)00189-7
更新日期：1998-07-01 00:00:00
abstract：:Reactive Oxygen Species (ROS) are crucial to multiple biological processes involved in the pathophysiology of inflammation, and are also involved in redox signaling responses. Although previous reports have described an association between oxidative events and the modulation of innate immunity, a role for redox signal...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2014.12.014
更新日期：2015-04-01 00:00:00
abstract：:Nore1A was originally identified as a potential Ras effector, and Nore1B is an alternatively spliced isoform. Both share a Ras/Rap association domain (RA domain) but only Nore1A contains sequence motifs that predict SH3 domain binding and diacylglycerol/phorbol ester binding in the amino-terminal region. Here we repor...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2006.01.015
更新日期：2006-10-01 00:00:00
