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 screen identified the ubiquitin carboxyl-terminal hydrolase-L1 (Uch-L1), a protein associated with Parkinson's disease, as alpha(2)AR interacting protein. This interaction was confirmed and evaluated by GST pull down assays demonstrating that Uch-L1 binds preferentially to the alpha(2A)AR subtype and only with less affinity to alpha(2B)AR and alpha(2C)AR. Co-immunoprecipitation of epitope-tagged proteins confirmed the specificity of this interaction in vivo. Moreover, co-transfection of a truncated G-protein coupled receptor kinase-DNA preventing alpha(2)AR phosphorylation led to an increased signal-strength of coimmunoprecipitated Uch-L1. Confocal laser microscopy showed that interaction of alpha(2A)AR and Uch-L1 occurred in the cytoplasm. alpha(2)AR agonist mediated activation of p44/42 MAP Kinase was drastically decreased in the presence of Uch-L1 indicating a functional relevance of this interaction. These findings may present a mechanism contributing to subtype-specific alpha(2)AR trafficking and a potential pathway for the neuroprotective effects of alpha(2)AR agonists.
journal_name
Cell Signaljournal_title
Cellular signallingauthors
Weber B,Schaper C,Wang Y,Scholz J,Bein Bdoi
10.1016/j.cellsig.2009.05.011subject
Has Abstractpub_date
2009-10-01 00:00:00pages
1513-21issue
10eissn
0898-6568issn
1873-3913pii
S0898-6568(09)00174-0journal_volume
21pub_type
杂志文章abstract::Activation of phosphatidylinositol (PI)-kinase is involved in the regulation of a wide array of cellular activities. The enzyme exists as a dimer, consisting of a catalytic and a regulatory subunit. Five isoforms of the regulatory subunit have been identified and classified into three groups comprising respectively 85...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/s0898-6568(99)00086-8
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abstract::Understanding how cells integrate signals from a variety of chemically diverse information-containing molecules into complex, orchestrated responses such as cell proliferation, differentiation and apoptosis is an overarching goal of cell biology. The ligand molecules that act upon cell surface receptors include those ...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/s0898-6568(97)00194-0
更新日期:1998-09-01 00:00:00
abstract::Epstein-Barr virus (EBV) encoded latent membrane protein 1 (LMP1) is essential for the immortalization of human B cells and is linked etiologically to several human tumors. LMP1 is an integral membrane protein which acts like a constitutively active receptor. It binds tumor necrosis factor (TNF)-receptor-associated fa...
journal_title:Cellular signalling
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doi:10.1016/j.cellsig.2004.03.014
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abstract::Lipopolysaccharide (LPS) has been shown to up-regulate the expression of vascular cell adhesion molecule (VCAM)-1 which contributes to the occurrence of airway inflammatory diseases. Genetic analysis reveals the existence of activator protein-1 (AP-1) binding site on VCAM-1 promoter region. However, the role of AP-1 i...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2009.04.006
更新日期:2009-09-01 00:00:00
abstract::The strong inhibition of thrombin-induced platelet functions induced by okadaic acid is not correlated with the partial modification of pleckstrin phosphorylation, which remains still phosphorylated two min after stimulation, indicating that protein kinase C is not affected by okadaic acid. We then investigated the ef...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/s0898-6568(96)00119-2
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abstract::Transforming growth factor-β1 (TGF-β1) regulates the tissue response to injury and is the principal driver of excessive scarring leading to fibrosis and eventual organ failure. The TGF-β1 effectors SMAD3 and p53 are major contributors to disease progression. While SMAD3 is an established pro-fibrotic factor, the role ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2014.02.017
更新日期:2014-07-01 00:00:00
abstract::The BRCA1 gene codes for a protein involved in the DNA double strand break (DDSB) repair. Alongside the dominant full-length splicing form of BRCA1, numerous endogenously expressed alternative splicing variants of unknown significance have been described in various tissues. Some of them retain the original BRCA1 readi...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2011.12.023
更新日期:2012-05-01 00:00:00
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
doi:10.1016/j.cellsig.2016.04.005
更新日期:2016-08-01 00:00:00
abstract::Self-renewing divisions of normal and cancerous stem cells are responsible for the initiation and maintenance of normal and certain cancerous tissues, respectively. Recent findings suggest that tumor surveillance mechanisms can reduce regenerative capacity and frequency of normal stem cells, thereby contributing to ti...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2007.06.021
更新日期:2007-12-01 00:00:00
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journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2009.05.001
更新日期:2009-11-01 00:00:00
abstract::CD44 is a hyaluronan binding cell surface signal transducing receptor that influences motility, cell survival and proliferation as well as the formation of tumor microenvironment. CD44 contains two variable regions encoded by variable exons. Alternative splicing, which is often deregulated in cancer, can produce vario...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2014.07.011
更新日期:2014-10-01 00:00:00
abstract::Clathrin-mediated endocytosis is a complex process regulated at many different levels. We showed previously that activation of the angiotensin type 1 receptor (AT1R), which belongs to the G protein-coupled receptor (GPCR) family, leads to c-Src-dependent tyrosine phosphorylation of beta2-adaptin, a subunit of the clat...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2008.09.013
更新日期:2009-01-01 00:00:00
abstract::Forkhead-associated domain (FHA) is a phosphopeptide recognition domain embedded in some regulatory proteins. With similar fold type to important eukaryotic signaling molecules such as Smad2 and IRF3, the role of bacterial FHA domain is intensively pursued. Reported bacterial FHA domain roles include: regulation of gl...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2012.11.019
更新日期:2013-03-01 00:00:00
abstract::Loss of p53's tumor-suppressive function, either via TP53 mutation or hyperactive p53 inhibitory proteins, is one of the most frequent events in the development of human cancer. Here, we describe a strategy of pharmacologically inhibiting iASPP, a negative regulator of p53, to restore wild-type p53's tumor-suppressive...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2019.109508
更新日期:2020-03-01 00:00:00
abstract::Mitogen-activated protein kinases (MAPKs) define a specific group of eukaryotic protein kinases which regulate a number of cellular functions by transducing extracellular signals to intracellular responses. Unlike other protein kinases, catalytic activation of MAPKs by MAPKKs depends on dual phosphorylation at two tyr...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2015.09.017
更新日期:2015-12-01 00:00:00
abstract::We previously showed that activated peroxisome proliferator-activated receptor (PPAR)β/δ can protect pancreatic β cells against lipotoxic apoptosis. However, the molecular mechanism remained unclear. Glucagon-like peptide-1 receptor (GLP-1R) has been reported to exhibit a protective effect against lipotoxic apoptosis ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2013.11.019
更新日期:2014-02-01 00:00:00
abstract::S6K1, a critical downstream substrate of mTORC1, has been implicated in regulating protein synthesis and a variety of processes that impinge upon cell growth and proliferation. While the role of the cytoplasmic p70(S6K1) isoform in the regulation of translation has been intensively studied, the targets and function of...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2011.03.016
更新日期:2011-08-01 00:00:00
abstract::Circulating symmetric dimethylarginine (SDMA) is increased in patients with chronic kidney disease. SDMA is considered an inert metabolite, but because it can transported into cells, we studied the effect of SDMA on glomerular endothelial cells. SDMA suppressed VEGF-induced endothelial nitric oxide synthase (eNOS) pho...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2014.09.024
更新日期:2015-01-01 00:00:00
abstract::The numerous examples of "crosstalk" between signal transduction pathways reported in the biochemical literature seem to imply a general common response of cells to different stimuli, even when these stimuli act initially on different cascades. This contradicts our knowledge of the specificity of action of extracellul...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/s0898-6568(01)00168-1
更新日期:2001-07-01 00:00:00
abstract::Although there is a substantial literature that mitochondria have a crucial role in the aging process, the mechanism has remained elusive. The role of reactive oxygen species, mitochondrial DNA injuries, and a decline in mitochondrial quality control has been proposed. Emerging studies have demonstrated that Krebs cyc...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2014.03.030
更新日期:2014-07-01 00:00:00
abstract::Akt (also known as protein kinase B or PKB) comprises three closely related isoforms Akt1, Akt2 and Akt3 (or PKBα/β/γ respectively). We have a very good understanding of the mechanisms by which Akt isoforms are activated by growth factors and other extracellular stimuli as well as by oncogenic mutations in key upstrea...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2011.05.004
更新日期:2011-10-01 00:00:00
abstract::How might a microbial cell that is entirely metabolically dormant - and which has the ability to remain so for extended periods of time - irreversibly commit itself to resuming vegetative growth within seconds of being exposed to certain amino acids or sugars? That this process takes place in the absence of any detect...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2020.109729
更新日期:2020-10-01 00:00:00
abstract::The immune modulator FTY720 is phosphorylated in vivo to FTY720 phosphate (FTY-P), which activates four sphingosine 1-phosphate (S1P) receptors including S1P(3). Upon activation with S1P, S1P(3) couples to G(i)- and G(q)-protein-dependent signalling pathways. Here we show that FTY-P selectively activates the S1P(3)-me...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2008.01.019
更新日期:2008-06-01 00:00:00
abstract::We investigated the effects of retinoic acid (RA) on the signalling pathways by prostaglandin E2 (PGE2) in osteoblast-like MC3T3-E1 cells. The pretreatment with RA significantly inhibited the formation of inositol phosphates induced by 10 microM PGE2 in a dose-dependent manner in the range between 0.1 nM and 0.1 micro...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/0898-6568(93)90080-6
更新日期:1993-07-01 00:00:00
abstract::Vav proteins are evolutionarily conserved from nematodes to mammals and play a pivotal role in many aspects of cellular signaling, coupling cell surface receptors to various effectors functions. In mammals, there are three family members; Vav1 is specifically expressed in the hematopoietic system, whereas Vav2 and Vav...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/s0898-6568(03)00110-4
更新日期:2004-01-01 00:00:00
abstract::Macrophages take up oxidized low density lipoprotein (oxLDL) after being exposed to it in the blood vessels. oxLDL transforms macrophages into foam cells, which are a hallmark of atherosclerosis. The effects that oxLDL have on the inflammatory responses of foam cells are not clear. Here, we investigated how oxLDL modu...
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::The activation of corticotrophin-releasing hormone receptor (CRHR) 1 is implicated in neuronal injury in experimental stroke. However, little is known about the relationship between CRHR1 activation and brain endothelial barrier impairment after ischemia and reperfusion (I/R). Recently we have demonstrated that the ac...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2019.109467
更新日期:2020-02-01 00:00:00
abstract::SCF induces autophosphorylation of Kit and activates a variety of signaling components including Jnks, Erks, PI 3 Kinase, the JAK-Stat pathway and members of the Src family. Previously we showed that Lyn is activated at multiple points during SCF-induced cell cycle progression and contributes to SCF-mediated growth, c...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2004.06.004
更新日期:2005-01-01 00:00:00
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 ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2007.05.015
更新日期:2007-10-01 00:00:00
abstract::Focal adhesion kinase (FAK) plays an important role in integrin-mediated signal transduction pathways and its C-terminal noncatalytic domain Fak-related non-kinase (FRNK), which is autonomously expressed, acts as an inhibitor of FAK. A model has been proposed where FAK and FRNK compete for an essential common binding ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/s0898-6568(01)00226-1
更新日期:2001-12-01 00:00:00