Abstract:
:Janus kinase 2 (Jak2) has a pivotal role in erythropoietin (Epo) signaling pathway, including erythrocyte differentiation and Stat5 activation. In the course of screening for critical phosphorylation of tyrosine residues in Jak2, we identified tyrosine 913 (Y(913)) as a novel and functional phosphorylation site, which negatively regulates Jak2. Phosphorylation at Y(913) rapidly occurred and was sustained for at least 120 min after Epo stimulation, in contrast to the transient phosphorylation of Y(1007/1008) in the activation loop of Jak2. Interestingly, phosphorylation defective mutation of Y(913) (Y(913)F) results in a significant enhancement of Epo-induced Jak2 activation, whereas phosphorylation mimic mutation of Y(913) (Y(913)E) completely abrogated its activation. Furthermore, Jak2 deficient fetal liver cells expressing Y(913)F mutant generated many mature erythroid BFU-E and CFU-E colonies, while Y(913)E mutant failed to reconstitute Jak2 deficiency. We also demonstrate, in Jak1, phosphorylation of Y(939), a corresponding tyrosine residue with Y(913), negatively regulated Jak1 signaling pathway. Accordingly, our results suggest that this tyrosine phosphorylation in JH1 domain may be involved in common negative regulation mechanism for Jak family.
journal_name
Cell Signaljournal_title
Cellular signallingauthors
Funakoshi-Tago M,Tago K,Kasahara T,Parganas E,Ihle JNdoi
10.1016/j.cellsig.2008.07.008subject
Has Abstractpub_date
2008-11-01 00:00:00pages
1995-2001issue
11eissn
0898-6568issn
1873-3913pii
S0898-6568(08)00215-5journal_volume
20pub_type
杂志文章abstract::Using adenoviruses encoding RGS2, RGS4 and Lsc (regulator of G protein signalling (RGS) domain of p115 RhoGEF), we investigated the contributions of G(q/11), Gi and G(12/13) proteins to G protein-coupled receptor (GPCR)-mediated activation of the extracellular signal-regulated kinase (ERK) pathway in adult rat ventric...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2004.10.008
更新日期:2005-05-01 00:00:00
abstract::HOX family transcription factors belong to a highly conserved subgroup of the homeobox superfamily that determines cellular fates in embryonic morphogenesis and the maintenance of adult tissue architecture. HOX family transcription factors play key roles in numerous cellular processes including cell growth, differenti...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2019.109469
更新日期:2020-02-01 00:00:00
abstract::Calcineurin (CnA) is an important signalling molecule in skeletal muscle, in the promotion of differentiation, slow-fibre phenotype and possibly fibre hypertrophy. We found that stable expression of constitutively active CnA in muscle C2C12 cells strongly activated NF-kappaB, a key mediator of muscle wasting. NF-kappa...
journal_title:Cellular signalling
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doi:10.1016/s0898-6568(02)00120-1
更新日期:2003-05-01 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
abstract::Through diametric actions, the transforming growth factor beta (TGFbeta) and Angiotensin II (AngII) play important roles in regulating various biological responses such as cell proliferation and migration. Signaling initiated by TGFbeta and AngII occurs through two structurally and functionally distinct receptor super...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2009.01.037
更新日期:2009-06-01 00:00:00
abstract::Transforming growth factor-β (TGF-β) signaling plays a key role in regulating normal cell growth and differentiation, and mutations affecting members of this pathway contribute to cancer development and metastasis. In DNA mismatch repair (MMR)-deficient colorectal cancers that exhibit the microsatellite instability (M...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2016.04.012
更新日期:2016-08-01 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::The ectodomain of TOLL-like receptors (TLR) is highly glycosylated with several N-linked gylcosylation sites located in the inner concave surface. The precise role of these sugar N-glycans in TLR receptor activation is unknown. Recently, we have shown that Neu1 sialidase and not Neu2, -3 and -4 forms a complex with TL...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2009.09.038
更新日期:2010-02-01 00:00:00
abstract::Induction of nitrosative stress has been observed in various cancer types and in tumor environment. However, it is still unclear how cancer cells combat the effect of nitrosative stress. The main targets of nitrosative stress in cells are cellular lipids, proteins and DNA. Autophagy or self-cleaning generates energy f...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2019.109411
更新日期:2019-12-01 00:00:00
abstract::We analysed the effects of high glucose in rat1 cells overexpressing insulin receptor. High (25 mM) glucose inhibited insulin-stimulated tyrosine kinase activity completely at insulin concentrations of 1 and 5 ng/ml. Decapeptides modelled on insulin receptor sequences surrounding serines 1035 and 1270 were found to in...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/s0898-6568(03)00090-1
更新日期:2004-01-01 00:00:00
abstract::Smac/DIABLO is a mitochondrial protein that participates in apoptotic cell death by means of sequestering several members of the inhibitor of apoptosis protein family. This action allows caspase activation, cleavage of key cellular substrates and death. Release from mitochondria is considered the main regulatory step ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2007.01.001
更新日期:2007-06-01 00:00:00
abstract::Phagocytosis is an essential event in the complex process of tissue repair. Here we examined the effect of low intensity pulsed ultrasound (US), which promotes fracture and wound healing, on phagocytosis by mouse macrophage cell line J774A.1 and human monocyte-derived macrophages. First, 10 to 40 min low intensity pul...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2007.12.005
更新日期:2008-04-01 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::We previously showed that protein kinase C (PKC) induces phosphatidylcholine-hydrolysing phospholipase D activation in osteoblast-like MC3T3-E1 cells and that tyrosine kinase is involved in this activation. Wortmannin, a potent inhibitor of phosphatidylinositol 3-kinase, markedly enhanced the formation of choline indu...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/0898-6568(94)00080-u
更新日期:1995-03-01 00:00:00
abstract::Interleukin-6-type cytokine receptors are expressed in polarized cells such as hepatocytes and intestinal cells. For the interleukin-6-receptor gp80 and its signal transducer gp130, a preferential basolateral localization was demonstrated in Madin-Darby canine kidney (MDCK) cells and two basolateral sorting signals we...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2005.09.006
更新日期:2006-08-01 00:00:00
abstract::C5L2 is a receptor that binds to C5a and belongs to the family of G protein-coupled receptors, but its role in physiological C5a-mediated responses remains under debate. Here we show that, like the canonical C5a receptor C5aR, C5L2 plays a pro-inflammatory role in a murine model of acute experimental colitis. We demon...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2014.02.021
更新日期:2014-07-01 00:00:00
abstract::In humans, thromboxane (TX) A(2) signals through the TPalpha and TPbeta isoforms of the TXA(2) receptor that exhibit common and distinct roles. For example, Gq/phospholipase (PL)Cbeta signaling by TPalpha is directly inhibited by the vasodilators prostacyclin and nitric oxide (NO) whereas that signaling by TPbeta is u...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2008.04.006
更新日期:2008-08-01 00:00:00
abstract::Integrin β6 (ITGB6), an epithelial-specific integrin, is upregulated in oral squamous cell carcinomas (OSCC) and is associated with progression and metastasis of OSCC. Lysophosphatidic acid (LPA), an important bioactive phospholipid present in saliva, has also been related to OSCC cell migration and invasiveness. LPA ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2019.04.008
更新日期:2019-08-01 00:00:00
abstract::Octimibate and related nonprostanoid prostacyclin mimetics are partial agonists displaying highly tissue-specific responses. Octimibate demonstrated considerably greater efficacy for stimulation of adenylyl cyclase activity in Chinese hamster ovary cells transiently expressing mouse prostacyclin receptors (mIP-CHO cel...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/s0898-6568(01)00210-8
更新日期:2001-11-01 00:00:00
abstract::RAW macrophages, which express the PDE4D3 and PDE4D5 cAMP phosphodiesterase isoforms, exhibited increased PDE4 activity when challenged with H2O2 in a fashion that was negated by treatment with the cell permeant antioxidant, N-acetyl cysteine and by diphenyleneiodonium chloride, an inhibitor of NADPH oxidase. In Cos1 ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2006.07.018
更新日期:2006-11-01 00:00:00
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2009.01.017
更新日期:2009-05-01 00:00:00
abstract::β-Adrenergic receptors (βAR) and D(2)-like dopamine receptors (which include D(2)-, D(3)- and D(4)-dopamine receptors) activate G(s) and G(i), the stimulatory and inhibitory heterotrimeric G proteins, respectively, which in turn regulate the activity of adenylyl cyclase (AC). β(2)-Adrenergic receptors (β(2)AR) and D(4...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2012.06.011
更新日期:2012-11-01 00:00:00
abstract::Endothelial cell apoptosis induced by hypoxia is implicated in the pathogenesis of vascular diseases. However, the underlying mechanism is not clearly elucidated. In this study, we found that hypoxia increased Mxi1-0 expression, and the Mxi1-0 siRNA could inhibit caspase-8 activation and apoptosis in HUVECs induced by...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2018.08.009
更新日期:2018-11-01 00:00:00
abstract::Formycin A (1.0 mM) caused a rapid, sustained and rapidly reversible inhibition of effluent radioactivity in rat pancreatic islets prelabelled with myo-[2-3H]inositol and perifused in the presence of 8.3 mM D-glucose. This coincided with a progressive decrease in islet ATP content and transient inhibition of insulin r...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/0898-6568(95)02009-8
更新日期:1995-11-01 00:00:00
abstract::The phosphatidylinositol (PI) 3-kinase family of enzymes is now known to be regulated by several different upstream pathways in response to virtually all growth factors and cytokines. In the past few years, the phosphoinositides phosphorylated at the 3-OH position of the inositol ring have been shown to be lipid secon...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/s0898-6568(97)00129-0
更新日期:1998-04-01 00:00:00
abstract::Sphingolipids and their synthetic enzymes have emerged as critical mediators in numerous diseases including inflammation, aging, and cancer. One enzyme in particular, sphingosine kinase (SK) and its product sphingosine-1-phosphate (S1P), has been extensively implicated in these processes. SK catalyzes the phosphorylat...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2020.109875
更新日期:2021-03-01 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::15-lipoxygenase (15-LO) is known to play an important role in chronic pulmonary hypertension. Accumulating evidence for its down-stream participants in the vasoconstriction and remodeling processes of pulmonary arteries, while how hypoxia regulates 15-LO/15-hydroxyeicosatetraenoic acid (15-HETE) to mediate hypoxic pul...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2012.06.007
更新日期:2012-10-01 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
pub_type: 杂志文章
doi:10.1016/s0898-6568(01)00159-0
更新日期:2001-06-01 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