Abstract：
:Human ether-à-go-go-related gene (hERG or Kv11.1) encodes the rapidly activated delayed rectifier K(+) current (I(Kr)) in the human heart. Potential regulation of hERG channel by protein tyrosine kinases (PTKs) is not understood. The present study was designed to investigate whether this channel is modulated by PTKs using whole-cell patch clamp technique, and immunoprecipitation and Western blot analysis in HEK 293 cells stably expressing hERG gene. We found that the broad-spectrum PTK inhibitor genistein (30 microM), the selective EGFR (epidermal growth factor receptor) kinase inhibitor AG556 (10 microM) and the Src-family kinase inhibitor PP2 (10 microM) remarkably inhibited hERG channel current (I(hERG)), and the effects were significantly countered by the protein tyrosine phosphatase (PTP) inhibitor orthovanadate (1 mM). Immunoprecipitation and Western blot analysis demonstrated that membrane protein tyrosine phosphorylation of hERG channels was reduced by genistein, AG556, and PP2. The reduction of hERG channel phosphorylation level by genistein, AG556 or PP2 was antagonized by orthovanadate. Single point mutation(s) of Y475A and/or Y611A dramatically attenuated the inhibitory effect of I(hERG) by PP2 and/or AG556. Our results demonstrate the novel information that I(hERG) is modulated not only by Src-family kinases, but also by EGFR kinases. Y475 and/or Y611 are likely the preferred phosphorylation sites. Regulation of hERG channels by PTKs modifies the channel activity and thus likely alters electrophysiological properties including action potential duration and cell excitability in human heart and neurons.
journal_name
Cell Signaljournal_title
Cellular signallingauthors
Zhang DY,Wang Y,Lau CP,Tse HF,Li GRdoi
10.1016/j.cellsig.2008.06.006subject
Has Abstractpub_date
2008-10-01 00:00:00pages
1815-21issue
10eissn
0898-6568issn
1873-3913pii
S0898-6568(08)00182-4journal_volume
20pub_type
杂志文章abstract：:The effects of ouabain and monensin upon basal and carbachol-stimulated inositol phospholipid breakdown in rat cerebral cortical miniprisms have been investigated. Basal inositol phospholipid breakdown was increased by both compounds at both 6 and 18 mM K+. Enhancement of the carbachol response at 6 mM, but not at 18 ...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/0898-6568(91)90046-w
更新日期：1991-01-01 00:00:00
abstract：:The mitotic inhibitor securin is degraded via the ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C)-Cdc20 after anaphase onset. This triggers activation of the mitotic protease separase and thereby sister chromatid separation. However, only a proportion of securin molecules are degraded at metaphase-anapha...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2016.07.005
更新日期：2016-10-01 00:00:00
abstract：:Regulator of G Protein Signalling (RGS) proteins impede heterotrimeric G protein signalling. RGS2 decreases cAMP production and appears to interact with both adenylyl cyclase (AC) and its stimulatory G protein Gs. We showed previously that Green Fluorescent Protein-tagged RGS2 (GFP-RGS2) localizes to the nucleus in HE...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2005.05.004
更新日期：2006-03-01 00:00:00
abstract：:Transforming growth factory beta (TGF-beta) is a potent growth inhibitor of epithelial cells. One of the strategies used to elucidate the anti-proliferative mode of action of TGF-beta is to find out whether the receptor-generated signals interact with components of the basic machinery of the cell cycle. In this study ...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/s0898-6568(97)89890-7
更新日期：1997-05-01 00:00:00
abstract：:Although endoplasmic reticulum (ER) stress induction by some anticancer drugs can lead to apoptotic death of cancer cells, combination therapy with other chemicals would be much more efficient. It has been reported that proteasome inhibitors could induce cancer cell death through ER-stress. Our study, however, showed ...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2011.01.010
更新日期：2011-05-01 00:00:00
abstract：:Glucuronyl C5-epimerase (Hsepi) catalyzes the conversion of glucuronic acid to iduronic acid in the process of heparan sulfate biosynthesis. Targeted interruption of the gene, Glce, in mice resulted in neonatal lethality with varied defects in organ development. To understand the underlying molecular mechanisms of the...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2018.11.010
更新日期：2019-02-01 00:00:00
abstract：:Mitogen-activated protein (MAP) kinase cascades are signal transduction pathways that play pivotal regulatory roles in the biosynthesis of pro-inflammatory cytokines. MAP kinase phosphatase (MKP)-1, an archetypal member of the MKP family, is essential for the dephosphorylation/deactivation of MAP kinases p38 and JNK. ...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2007.03.013
更新日期：2007-07-01 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：:Heterotrimeric G proteins typically transduce signals from G protein-coupled receptors (GPCRs) to effector proteins. In the conventional G protein signaling paradigm, the G protein is located at the cytoplasmic surface of the plasma membrane, where, after activation by an agonist-bound GPCR, the GTP-bound Gα and free ...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2011.08.014
更新日期：2012-01-01 00:00:00
abstract：:In extracts of human platelets, three isoenzymes of cyclic nucleotide phosphodiesterase (PDE), namely, PDE2, PDE3, and PDE5, were identified; activities of PDE1 and PDE4 were not detected. In human platelets, the cGMP-hydrolytic activity was about six times higher than the cAMP-hydrolytic activity, and PDE5 and PDE3 a...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/s0898-6568(96)00112-x
更新日期：1996-12-01 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：: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：:Induction of apoptosis in Hep3B hepatoma cells by transforming growth factor beta 1 (TGF-beta 1) was accompanied by the activation of interleukin-1-beta-converting-enzyme-like proteases, which have recently been renamed as caspases. The caspase inhibitor ZVAD-FMK, which has a broader specificity for caspase family pro...
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：:Proteoglycans (PGs) represent a large proportion of the components that constitute the extracellular matrix (ECM). They are a diverse group of glycoproteins characterized by a covalent link to a specific glycosaminoglycan type. As part of the ECM, heparan sulfate (HS)PGs participate in both physiological and pathologi...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2020.109822
更新日期：2021-01-01 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
abstract：:Bladder cancer (BC) is one of the most common tumours of the urinary system and is also known as a highly malignant tumour. In addition to conventional diagnosis and treatment methods, recent research has focused on studying the molecular mechanisms related to BC, in the hope that new, less toxic and effective targete...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2020.109886
更新日期：2021-03-01 00:00:00
abstract：:The glucose-regulated protein grp78 gene is rapidly transactivated in 9L rat brain tumour (RBT) cells treated with okadaic acid (OA) followed by heat shock (HS) (termed OA-->HS treatment). By Northern blotting analyses and transient transfection assays, we herein show that transactivation of grp78 by OA-->HS is abolis...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/s0898-6568(02)00055-4
更新日期：2003-01-01 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：:Protectin DX (PDX), which is a novel regulator of 5' adenosine monophosphate-activated protein kinase (AMPK), has recently gained attention for its ability to improve several metabolic diseases. However, the function of PDX in vascular endothelial cells remains unclear. To confirm the protective effects of PDX on endo...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2018.09.011
更新日期：2019-01-01 00:00:00
abstract：:Interleukin-1 (IL-1) is the major prototypic proinflammatory cytokine that stimulates degradation of cartilage in arthritis by inducing prominent collagen II-degrading matrix metalloproteinase-13 (MMP-13). Nothing is known about the involvement of adaptor proteins, MyD88, IRAK1 and TRAF6 in MMP-13 regulation. Here we ...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2007.08.013
更新日期：2007-12-01 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
abstract：:Reelin is a secreted glycoprotein and essential for brain development and plasticity. Recent studies provide evidence that Reelin modifies platelet actin cytoskeletal dynamics. In this study we sought to dissect the contribution of Reelin in arterial thrombus formation. Here we analyzed the impact of Reelin in arteria...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2017.09.016
更新日期：2017-12-01 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：: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：:In this work, we used colon carcinoma cell-line HCT116 to study the involvement of the 86-kDa subunit (Ku86) of DNA-protein kinase (DNA-PK) in human tumoural cell proliferation. We transfected these cells with a 639-bp cDNA encoding a Ku86 portion inserted into pcDNA3.1 vector in the antisense orientation. After selec...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/s0898-6568(00)00126-1
更新日期：2000-12-01 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：:We found that CKD712, an S enantiomer of YS49, strongly inhibited inducible nitric oxide synthase (iNOS) and NO induction but showed a weak inhibitory effect on cyclooxygenase-2 (COX-2) and PGE(2) induction in LPS-stimulated RAW 264.7 cells. We, therefore, investigated the molecular mechanism(s) responsible for this b...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2008.06.012
更新日期：2008-10-01 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：:Rho GTPases are molecular switches involved in the regulation of many cellular processes. This review summarizes work examining how stimulation of receptor tyrosine kinases (RTKs) leads to the activation of Rho guanine nucleotide exchange factors (GEFs) and their Rho GTPase substrates. The collective findings strongly...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2006.01.022
更新日期：2006-11-01 00:00:00
abstract：:Embryonic stem cells (ESC) are pluripotent and could be maintained in vitro in a self-renewing state indefinitely, at the same time preserving their potential to differentiate towards more specific lineages. Despite the progress in the field, the complex network of signalling cascades involved in the maintenance of th...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2008.12.005
更新日期：2009-04-01 00:00:00
