Abstract:
:Macrophages play many different roles in tissue inflammation and immunity, and the plasticity of macrophage polarization is closely associated with acute inflammatory responses. O-GlcNAcylation is an important type of post-translational modification, which subtly modulates inflammation responses. Transforming growth factor (TGF)-β-activated kinase 1 (TAK1) is a key serine/threonine protein kinase that mediates signals transduced by pro-inflammatory cytokines such as TGF-β, tumor necrosis factor (TNF), and interleukin-1 (IL-1). It is here reported that TGFβ-activated kinase (TAK1) is modified with N-acetylglucosamine (O-GlcNAc) on S427. Both IL-1 and osmotic stress, which are known as the TAK1-signaling inducers, significantly trigger the O-GlcNAcylation of TAK1 in macrophages. By overexpressing wild-type (WT) or S427A TAK1 mutant into macrophages, it was determined that O-GlcNAcylation of TAK1 on S427 is required for T187/S192 phosphorylation and full activation of TAK1 upon stimulation with IL-1α and NaCl. Aborting O-GlcNAcylation of TAK1 on S427 was found to inhibit the downstream JNK and nuclear factor-κB activation and reduce the final amount of cytokines produced in activated macrophages to a great extent. Results also showed that overexpression of the O-GlcNAcylation-deficient mutant of TAK1 promotes LPS-mediated apoptosis in macrophages. Importantly, TAK1 O-GlcNAcylation was found to promote M1 macrophage polarization in activated macrophages. Taken together, these data demonstrate that O-GlcNAcylation of TAK1 on S427 critically regulates the pro-inflammatory activation and M1 polarization of macrophages via modulation of the TAK1/JNK/NF-κB signaling pathway.
journal_name
Cell Signaljournal_title
Cellular signallingauthors
Zhang D,Xu Z,Tao T,Liu X,Sun X,Ji Y,Han L,Qiu H,Zhu G,Shen Y,Zhu L,Shen Adoi
10.1016/j.cellsig.2016.08.008subject
Has Abstractpub_date
2016-11-01 00:00:00pages
1742-52issue
11eissn
0898-6568issn
1873-3913pii
S0898-6568(16)30206-6journal_volume
28pub_type
杂志文章,收录出版abstract::In eukaryotes, proper loading and activation of MCM helicase at chromosomal origins plays a central role in DNA replication. Activation of MCM helicase requires its association with CDC45-GINS complex, but the mechanism of how this complex activates MCM helicase is poorly understood. Here we identified SIK1 (salt-indu...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2016.08.018
更新日期:2016-12-01 00:00:00
abstract::To investigate whether G protein-coupled receptor kinases (GRKs) are involved in the regulation of the PTH/PTHrPR, we have established mutant SaOS-2 cells which stably overexpress (> 10-20-fold) a dominant negative form of the beta-adrenergic receptor kinase-1 (beta ARK-1). Acute (< or = 2 h) incubation with hPTH (1-3...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/s0898-6568(97)00044-2
更新日期:1997-09-01 00:00:00
abstract::In humans injured myocardium cannot avert the onset and progression of ventricular dysfunction because of limited regenerative ability of myocytes. Although limited renaissance of cardiomyocytes has been reported in human infarcted hearts, it is generally accredited that non-functional fibrous tissue replaces the dead...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2013.01.027
更新日期:2013-05-01 00:00:00
abstract::Differential regulation of PLC-beta 1 and -beta 2 by the G-protein alpha-subunit, G alpha 11, and by G-protein beta gamma-subunits was studied utilizing recombinant PLC-beta 1 and -beta 2. Rat PLC-beta 1 and human PLC-beta 2 were purified after recombinant baculovirus-mediated expression in Sf9 cells. The catalytic pr...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/0898-6568(95)00039-r
更新日期:1995-09-01 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::β-Arrestins are multifunctional adaptor proteins best know for their vital role in regulating G protein coupled receptor (GPCR) trafficking and signaling. β-arrestin2 recruitment and receptor internalization of corticotropin-releasing factor receptor 1 (CRFR1), a GPCR whose antagonists have been shown to demonstrate b...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2019.109361
更新日期:2019-11-01 00:00:00
abstract::Here we demonstrate that elevation of cyclic AMP (cAMP) levels in human umbilical vein endothelial cells (HUVECs) specifically attenuates ERK1,2 activation in response to either leptin or a soluble interleukin IL-6 receptor-alpha/IL-6 (sIL-6R alpha/IL-6) trans-signalling complex but not protein kinase C activator phor...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2009.07.009
更新日期:2009-11-01 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::Cross-talk between nuclear receptors involved in the control of drug metabolism is being increasingly recognised as a source of drug side effects. Omeprazole is a well known activator of the aryl hydrocarbon receptor (AhR). We investigated the regulation of AhR by omeprazole-sulphide, a degradation metabolite of omepr...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2005.07.007
更新日期:2006-05-01 00:00:00
abstract::Dystrophin and the dystrophin-associated protein complex (DAPC) have recently been implicated in cell signalling events. These proteins are ideally placed to transduce signals from the extracellular matrix (ECM) to the cytoskeleton. Here we show that beta-dystroglycan is tyrosine-phosphorylated in C2/C4 mouse myotubes...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/s0898-6568(01)00188-7
更新日期:2001-09-01 00:00:00
abstract::Previous studies implicating a role for protein kinase C (PKC) in mediating stimulation of cellular responses by physiological agonists have relied on use of non-specific inhibitors or direct stimulation of PKC by phorbol esters. However, much of this evidence is questionable. Here, we have investigated the effects of...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/s0898-6568(96)00097-6
更新日期:1997-01-01 00:00:00
abstract::Thrombopoietin (TPO) and its receptor (c-Mpl) are the major regulators of megakaryocyte and platelet production and serve a critical and non-redundant role in hematopoietic stem cell (HSC) biology. TPO signals through the Jak-STAT, Ras-Raf-MAPK, and PI3K pathways, and promotes survival, proliferation, and polyploidiza...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2005.09.010
更新日期:2006-08-01 00:00:00
abstract::Protein-tyrosine phosphatases (PTPases) play an essential role in the regulation of reversible tyrosine phosphorylation of cellular proteins that mediate insulin action. In order to explore the potential role of the transmembrane PTPase (LAR) in insulin receptor signal transduction, we overexpressed the full-length LA...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/s0898-6568(96)00101-5
更新日期:1996-11-01 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::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::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::In fura-2 loaded isolated mouse pancreatic acinar cells, xanthine oxidase (XOD)-catalyzed reactive oxygen species (ROS) generation caused an increase in the cytosolic Ca(2+) concentration ([Ca(2+)](i)) by release of Ca(2+) from intracellular stores. The ROS-induced Ca(2+) signals showed large variability in shape and ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/s0898-6568(01)00247-9
更新日期:2002-02-01 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::Aggregation of the high-affinity receptor for IgE (Fc eta RI) on the surface of intact or permeabilized rodent mast cells results in tyrosine phosphorylation of phospholipase C-gamma 1 (PLC gamma 1) and PLC gamma 2, and translocation of both isozymes to the particulate fraction. We report here that activation of resid...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/s0898-6568(96)00073-3
更新日期:1996-09-01 00:00:00
abstract::The discovery of new signalling pathways is always followed by the development of pharmacological agents as drugs that can be used in the treatment of diseases resulting from a dysfunction of the signalling pathway in question. Apelin signalling plays a role in the central and peripheral regulation of the cardiovascul...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2004.09.018
更新日期:2005-04-01 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
更新日期:1997-01-01 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::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:BACKGROUND:Bronchial fibroblasts are the main structural cells responsible for extracellular matrix production and turnover in lung tissue. They play a key role in airway remodelling in asthma through different cytokines including interleukin (IL-6). OBJECTIVE:To decipher IL-6 signalling in bronchial fibroblasts obtai...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2017.12.001
更新日期:2018-03-01 00:00:00
abstract::C1-Ten is a member of the tensin family of focal adhesion molecules but recent studies suggest it plays a more active role in many biological processes because of its potential association with diabetes and cancers. However, relatively little is known about the regulation of C1-Ten, such as changes in its protein leve...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2014.07.033
更新日期:2014-11-01 00:00:00
abstract::p130Cas/breast cancer anti-oestrogen resistance 1 (BCAR1) is a member of the Cas (Crk-associated substrate) family of adaptor proteins, which have emerged as key signalling nodes capable of interactions with multiple proteins, with important regulatory roles in normal and pathological cell function. The Cas family of ...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2012.12.019
更新日期:2013-04-01 00:00:00
abstract::Labelling with [3H]glucosamine was used to prepare a transforming growth factor-beta 1 (TGF-beta 1)-sensitive glycosylphosphatidylinositol (GPI) from monolayer cultures of rabbit articular chondrocytes (RAC), which may be involved in control of the cell cycle. The polar headgroup of this glycosylphosphatidylinositol w...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/0898-6568(94)90074-4
更新日期:1994-02-01 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::The role of the ras oncogene in the signalling pathway triggered by platelet-derived growth factor BB (PDGF-BB) has been investigated in a cell line which normally differentiates into myotubes. Following the activation of the N-ras oncogene, however, the cells proliferate and form foci. PDGF-BB stimulated the phosphor...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/0898-6568(94)00082-m
更新日期:1995-03-01 00:00:00
abstract::Tyrosine phosphorylation (Tyr-P) of focal adhesion kinase (FAK) regulates FAK activation. Phosphorylated FAK Tyr 397 binds Src family kinases (Src), which in turn directly phosphorylate FAK Tyr 576/577 to produce maximal FAK enzymatic activity. CB₁ cannabinoid receptors (CB₁) are abundantly expressed in the nervous sy...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2013.03.020
更新日期:2013-08-01 00:00:00