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)-mediated and G(i)-coupled inhibition of adenylyl cyclase. Contemporaneously, it antagonizes the S1P-induced activation of G(q) via S1P(3) in intracellular calcium flux measurements, GTP-binding experiments, and flow cytometric analyses of activation-induced receptor down-regulation. In contrast to S1P, pre-treatment with FTY-P did not desensitize S1P-induced calcium flux or chemotaxis via S1P(3). The lack of receptor desensitization prevented S1P(3)-mediated migration to FTY-P. Human umbilical vein endothelial cells express S1P(1) and S1P(3), and respond to S1P and FTY-P by ERK1/2 phosphorylation and by intracellular calcium release in a pertussis toxin-sensitive manner. But whereas a mixture of S1P and FTY-P was not affecting ERK1/2 phosphorylation, the intracellular calcium flux was hampered with increasing amounts of FTY-P, which points to a cross-talk between S1P(1) and S1P(3). FTY-P is therefore one of the rare ligands which bind to a receptor that couples multiple G-proteins but selectively activates only one signalling pathway.
journal_name
Cell Signaljournal_title
Cellular signallingauthors
Sensken SC,Stäubert C,Keul P,Levkau B,Schöneberg T,Gräler MHdoi
10.1016/j.cellsig.2008.01.019subject
Has Abstractpub_date
2008-06-01 00:00:00pages
1125-33issue
6eissn
0898-6568issn
1873-3913pii
S0898-6568(08)00039-9journal_volume
20pub_type
杂志文章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：:Although increasing evidence demonstrated that deregulation of mircoRNA-503 (miRNA-503) contributes to tumorigenesis, little is known about the biological role and intrinsic regulatory mechanisms of miR-503 in prostate cancer (PCa). In present study, we found that miR-503 was significantly downregulated in advanced PC...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2016.06.002
更新日期：2016-09-01 00:00:00
abstract：:In this study, we showed that nitric oxide (NO) donors induced the mesangial cell proliferation and cyclooxygenase-2 (COX-2) protein expression in murine mesangial cells. An inflammatory condition [lipopolysaccharide (LPS) plus interferon-gamma (IFN-gamma)] could also induce cell proliferation and significantly enhanc...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2004.11.015
更新日期：2005-08-01 00:00:00
abstract：:The dual-specificity mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) inactivates MAP kinases by dephosphorylation. Here we show that the proinflammatory cytokine interleukin (IL)-17A induces adult mouse primary cardiac fibroblast (CF) proliferation and migration via IL-17 receptor A//IL-17 receptor C-dep...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2011.10.010
更新日期：2012-02-01 00:00:00
abstract：:Src homology (SH) 3 domains are small modules found in a diverse array of proteins. The presence of an SH3 domain confers upon its resident protein the ability to interact with specific proline-rich sequences in protein binding partners. A major focus of research has highlighted a role for SH3 domain-mediated interact...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/s0898-6568(98)00059-x
更新日期：1999-04-01 00:00:00
abstract：:The possible involvement of zeta isozyme of protein kinase C (PKC zeta) in phorbol ester-induced signal transduction was investigated in mouse epidermal cells. Western blot analysis of RESOURCE Q column chromatography eluates obtained from 105,000 g supernatants and particulate fractions of epidermal cells was perform...
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：: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：:SHP1 and SHP2 tyrosine phosphatases have both been implicated in signalling pathways downstream of the interleukin-3 (IL-3) receptor. We have investigated the co-association of SHP1 and SHP2 with tyrosine-phosphorylated proteins in IL-3-dependent BaF/3 cells. We demonstrate that both SHP1 and SHP2 associate with Aic2A...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/s0898-6568(01)00241-8
更新日期：2002-03-01 00:00:00
abstract：:Activation of the caspase proteases by c-Jun N-terminal kinase 1 (JNK1) has been proposed as a mechanism of apoptotic cell death. Here we report that insulin activates caspase-3 by a pathway requiring phosphatidylinositol 3'-kinase (PI3-kinase). JNK1 assays demonstrated that insulin treatment of myeloma cells induced ...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/s0898-6568(98)00024-2
更新日期：1999-01-01 00:00:00
abstract：:CK1δ and CK1ε are unique in the casein kinase 1 family and play critical roles in a number of physiological intracellular pathways. In particular, these kinases are involved in composing the mammalian circadian clock by phosphorylating core clock proteins. Considering that CK1δ/ε phosphorylate other key biological mol...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2016.12.010
更新日期：2017-02-01 00:00:00
abstract：:Caveolin-1 (Cav-1) is a major structural protein of caveolae and plays an important role as a negative regulator of various signaling pathways such as the transforming growth factor-beta (TGF-beta)/smad pathway. In this study, we investigated the role of cav-1 on basal and TGF-beta1-induced expression of type I procol...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2008.02.020
更新日期：2008-07-01 00:00:00
abstract：:In vitro, little specificity is seen for modulation of effectors by different combinations of Gbetagamma subunits from heterotrimeric G proteins. Here, we demonstrate that the coupling of specific combinations of Gbetagamma subunits to different receptors leads to a differential ability to modulate effectors in vivo. ...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/s0898-6568(00)00118-2
更新日期：2000-10-01 00:00:00
abstract：:Nitric oxide (NO) is known to regulate redox-sensitive signalling pathways in physiology and pathophysiology. Depending on its concentration, the NO-releasing compound S-nitrosoglutathione (GSNO) causes negative and positive regulation of thymocyte apoptosis. At levels below 0.6 mM, GSNO produces deoxyribonucleic acid...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/0898-6568(95)02051-9
更新日期：1996-03-01 00:00:00
abstract：:The endogenous circadian clock functions to maintain optimal physiological health through the tissue specific coordination of gene expression and synchronization between tissues of metabolic processes throughout the 24 hour day. Individuals face numerous challenges to circadian function on a daily basis resulting in s...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2020.109904
更新日期：2020-12-25 00:00:00
abstract：:Circular RNAs (circRNAs) belong to a diverse class of stable RNAs expressed in all cell types. Their proposed functions include sponging of microRNAs (miRNAs), sequestration and trafficking of proteins, assembly of multimeric complexes, production of peptides, and regulation of transcription. Backsplicing due to RNA s...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2020.109696
更新日期：2020-09-01 00:00:00
abstract：:The present study has examined the effects of adenosine A1 receptors on second messenger processes in GH3 cells. A1 receptors are present which are shown to inhibit adenylate cyclase in a GTP-requiring manner. Hormone (VIP) stimulation is also absolutely required for the observation of inhibition. Adenosine A1 recepto...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/0898-6568(89)90023-5
更新日期：1989-01-01 00:00:00
abstract：:Disruption of autophagy plays an import role in neurodegenerative disorders, where deficient elimination of abnormal and toxic protein aggregates promotes cellular stress, failure and death. Therefore, induction of autophagy has been proposed as a reasonable strategy to help neurons clear abnormal protein aggregates a...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2014.08.019
更新日期：2014-12-01 00:00:00
abstract：:Extracellular adenine dinucleotides are modulators of blood vessel tone. We have previously demonstrated that Ap(2)A and Ap(4)A induce the synthesis of nitric oxide (NO) from bovine aortic endothelial cells (BAEC) while Ap(3)A and Ap(5)A do not [FEBS Lett. 427 (1998) 320; Arch. Biochem. Biophys. 364 (1999) 280.]. In t...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/s0898-6568(00)00147-9
更新日期：2001-02-01 00:00:00
abstract：:Somatostatin receptors (SSTRs) are known to mediate diverse cellular responses. Most target cell express more than one SSTR isoform, making it difficult to define the signalling pathway used by individual receptor subtypes. Thus, we have expressed SSTR1 or SSTR2 in rat pituitary F4C1 cells which lack endogenous SSTRs....
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/s0898-6568(99)00019-4
更新日期：1999-07-01 00:00:00
abstract：:We have previously demonstrated the existence of two phenotypically distinct cell subsets in estrogen receptor (ER)-positive breast cancer (BC) based on their differential response to a Sox2 reporter (SRR2), with reporter responsive (RR) cells being more tumorigenic and stem-like than reporter unresponsive (RU) cells....
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2015.11.004
更新日期：2016-02-01 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：:The interferon regulated transcription factor IRF-1 is a tumour suppressor protein that is activated in response to viral infection and cell signalling activated by double stranded DNA lesions. IRF-1 has a short half-life (t(0.5) 20-40 min) allowing rapid changes in steady state levels by modulating its rate of degrad...
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 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：:The kidney is one of the fastest-aging organs, and renal senescence has become a major disease affecting human health. Renal cellular senescence is regulated by the joint action of multiple signal transduction pathways. The previous study by our research group found that the Janus kinase 2 (JAK2)/signal transducer and...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2018.10.021
更新日期：2019-01-01 00:00:00
abstract：:It has been shown lately that activity of G protein-coupled receptors (GPCRs) is regulated by an array of proteins binding to carboxy (C)-terminus of GPCRs. Proteins of 4.1 family are subsets of subcortical cytoskeletal proteins and are known to stabilize cellular structures and proteins at the plasma membrane. One of...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2012.11.020
更新日期：2013-03-01 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：:Intracellular calcium signaling pathways play a major role in cellular responses such as proliferation, differentiation and apoptosis. Human embryonic stem cells (hESC) provide new possibilities to explore the development and differentiation of various cell types of the human body. Intracellular calcium responses to v...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2012.12.024
更新日期：2013-04-01 00:00:00
abstract：:Exogenous tritiated phosphatidylinositol bisphosphate added to antennal preparations from locust and cockroach was hydrolysed releasing inositol trisphosphate. High activity of phospholipase C was detected in the soluble as well as in the membrane fraction. At low free calcium concentrations hydrolysis of the labelled...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/0898-6568(90)90032-6
更新日期：1990-01-01 00:00:00
abstract：:The induction of cytolytic activity in PC60, a murine T-cell hybridoma, is paralleled by a rise in the level of BLT-esterase (N-alpha-benzyloxycarbonyl-L-lysine thiobenzyl esterase), a serine esterase specific for activated T-cells. Both interleukin-1 (IL-1) and dibutyryl cAMP were albe to increase the esterase activi...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/0898-6568(90)90045-c
更新日期：1990-01-01 00:00:00
abstract：:In order to elucidate the molecular events in signal transduction, examination of the interaction between Ras and Raf-1 seems crucial. Many Raf-1 mutants have been investigated in terms of their binding activities to Ras, where only a few Ras mutants have been examined thus far. We have investigated the Raf-1-binding ...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/0898-6568(96)00078-2
更新日期：1996-08-01 00:00:00
