scholarly journals Evidence That Dynamin-2 Functions as a Signal-Transducing Gtpase

2000 ◽  
Vol 150 (1) ◽  
pp. 145-154 ◽  
Author(s):  
Kenneth N. Fish ◽  
Sandra L. Schmid ◽  
Hanna Damke
Keyword(s):  
Signal Transduction ◽  
Signal Transduction Pathway ◽  
Fold Increase ◽  
Protein Levels ◽  
Rich Domain ◽  
Dividing Cells ◽  
Additional Support ◽  
Transcription Factor P53 ◽  
New Evidence ◽  
Dynamin 2

The role of dynamin GTPases in the regulation of receptor-mediated endocytosis is well established. Here, we present new evidence that the ubiquitously expressed isoform dynamin-2 (dyn2) can also function in a signal transduction pathway(s). A ≤5-fold increase of dyn2 relative to endogenous levels activates the transcription factor p53 and induces apoptosis, as demonstrated by reduced cell proliferation, DNA fragmentation, and caspase-3 activation. Dyn2-triggered apoptosis occurs only in dividing cells and is p53 dependent. A mutant defective in GTP binding does not trigger apoptosis, indicating that increased levels of dyn2·GTP, rather than protein levels per se, are required to transduce signals that activate p53. A truncated dyn2 lacking the COOH-terminal proline/arginine-rich domain (PRD), which interacts with many SH3 domain-containing partners implicated in both endocytosis and signal transduction, triggers apoptosis even more potently than the wild-type. This observation provides additional support for the importance of the NH2-terminal GTPase domain for the apoptotic phenotype. All described effects are dyn2-specific because >200-fold overexpression of dyn1, the 70% identical neuronal isoform, has no effect. Our data suggest that dyn2 can act as a signal transducing GTPase affecting transcriptional regulation.

scholarly journals [6]-Gingerol Prevents Disassembly of Cell Junctions and Activities of MMPs in Invasive Human Pancreas Cancer Cells through ERK/NF-κB/Snail Signal Transduction Pathway

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Sung Ok Kim ◽  
Mi Ryeo Kim
Keyword(s):  
Signal Transduction ◽  
Nuclear Translocation ◽  
Signal Transduction Pathway ◽  
Cancer Cell Line ◽  
Duct Cell ◽  
Cell Junctions ◽  
Human Pancreas ◽  
Erk Pathway ◽  
Protein Levels ◽  
Extracellular Signal

To study the effects of [6]-gingerol, a ginger phytochemical, on tight junction (TJ) molecules, we investigated TJ tightening and signal transduction pathways in human pancreatic duct cell-derived cancer cell line PANC-1. The following methods were utilized: MTT assay to determine cytotoxicity; zymography to examine matrix metalloproteinase (MMP) activities; transepithelial electrical resistance (TER) and paracellular flux for TJ measurement; RT-PCR and immunoblotting for proteins related to TJ and invasion; and EMSA for NF-κB activity in PANC-1 cells. Results revealed that TER significantly increased and claudin 4 and MMP-9 decreased compared to those of the control. TJ protein levels, including zonula occludens (ZO-) 1, occludin, and E-cadherin, increased in [6]-gingerol-treated cells, which correlated with a decrease in paracellular flux and MMP activity. Furthermore, NF-κB/Snail nuclear translocation was suppressed via downregulation of the extracellular signal-regulated kinase (ERK) pathway in response to [6]-gingerol treatment. Moreover, treatment with U0126, an ERK inhibitor, completely blocked NF-κB activity. In conclusion, these findings demonstrate that [6]-gingerol regulates TJ-related proteins and suppresses invasion and metastasis through NF-κB/Snail inhibition via inhibition of the ERK pathway. Therefore, [6]-gingerol may suppress the invasive activity of PANC-1 cells.

scholarly journals The β-Arrestin-Like Protein Rim8 Is Hyperphosphorylated and Complexes with Rim21 and Rim101 To Promote Adaptation to Neutral-Alkaline pH

2012 ◽  
Vol 11 (5) ◽  
pp. 683-693 ◽  
Author(s):  
Jonathan Gomez-Raja ◽  
Dana A. Davis
Keyword(s):  
Signal Transduction ◽  
Transcription Factor ◽  
G Protein ◽  
Signal Transduction Pathway ◽  
Multivesicular Bodies ◽  
Ph Sensing ◽  
Content Type ◽  
Protein Levels ◽  
G Protein Coupled

ABSTRACTβ-Arrestin proteins are critical for G-protein-coupled receptor desensitization and turnover. However, β-arrestins have recently been shown to play direct roles in nonheterotrimeric G-protein signal transduction. TheCandida albicansβ-arrestin-like protein Rim8 is required for activation of the Rim101 pH-sensing pathway and for pathogenesis. We have found thatC. albicansRim8 is posttranslationally modified by phosphorylation and specific phosphorylation states are associated with activation of the pH-sensing pathway. Rim8 associated with both the receptor Rim21 and the transcription factor Rim101, suggesting that Rim8 bridges the signaling and activation steps of the pathway. Finally, upon activation of the Rim101 transcription factor,C. albicansRim8 was transcriptionally repressed and Rim8 protein levels were rapidly reduced. Our studies suggest that Rim8 is taken up into multivesicular bodies and degraded within the vacuole. In total, our results reveal a novel mechanism for tightly regulating the activity of a signal transduction pathway. Although the role of β-arrestin proteins in mammalian signal transduction pathways has been demonstrated, relatively little is known about how β-arrestins contribute to signal transduction. Our analyses provide some insights into potential roles.

scholarly journals Dual signal transduction pathways activated by TSH receptors in rat primary tanycyte cultures

2015 ◽  
Vol 54 (3) ◽  
pp. 241-250 ◽  
Author(s):  
Matei Bolborea ◽  
Gisela Helfer ◽  
Francis J P Ebling ◽  
Perry Barrett
Keyword(s):  
Signal Transduction ◽  
Signal Transduction Pathway ◽  
Fold Increase ◽  
Multiple Roles ◽  
Pars Tuberalis ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Metabolic Physiology ◽  
Tsh Secretion ◽  
Old Rats

Tanycytes play multiple roles in hypothalamic functions, including sensing peripheral nutrients and metabolic hormones, regulating neurosecretion and mediating seasonal cycles of reproduction and metabolic physiology. This last function reflects the expression of TSH receptors in tanycytes, which detect photoperiod-regulated changes in TSH secretion from the neighbouringpars tuberalis. The present overall aim was to determine the signal transduction pathway by which TSH signals in tanycytes. Expression of the TSH receptor in tanycytes of 10-day-old Sprague Dawley rats was observed byin situhybridisation. Primary ependymal cell cultures prepared from 10-day-old rats were found by immunohistochemistry to express vimentin but not GFAP and by PCR to express mRNA forDio2,Gpr50,Darpp-32andTshreceptors that are characteristic of tanycytes. Treatment of primary tanycyte/ependymal cultures with TSH (100 IU/l) increased cAMP as assessed by ELISA and induced a cAMP-independent increase in the phosphorylation of ERK1/2 as assessed by western blot analysis. Furthermore, TSH (100 IU/l) stimulated a 2.17-fold increase inDio2mRNA expression. We conclude that TSH signal transduction in cultured tanycytes signals via Gαsto increase cAMP and via an alternative G protein to increase phosphorylation of ERK1/2.

CK2 Is Acting Upstream of MEK3/6 as a Part of the Signal Control of ERK1/2 and p38 MAPK during Keratinocytes Autocrine Differentiation

2011 ◽  
Vol 66 (1-2) ◽  
pp. 83-86 ◽  
Author(s):  
Antonia R. Isaeva ◽  
Vanio I. Mitev
Keyword(s):  
Signal Transduction ◽  
P38 Mapk ◽  
Mammalian Cells ◽  
Protein Kinase Ck2 ◽  
Cell Signalling ◽  
Signal Transduction Pathway ◽  
Signal Control ◽  
Transduction Pathway ◽  
Protein Levels ◽  
Kinase Ck2

Protein kinase CK2 (formerly termed “casein kinase II”) is a ubiquitously in mammalian cells distributed Ser/Thr kinase, with global role in cell regulation. Although, the involvement of CK2 in cell signalling is vast-investigated, virtually nothing is known about its contribution to signal control of keratinocytes differentiation. Here we show that, in autocrine differentiating keratinocytes, inhibition of the CK2 activity induced by 4,5,6,7-tetrabromobenzotriazole (TBB) causes reciprocal changes in the activities of major signal transduction regulators of keratinocytes differentiation, i.e. ERK1/2 and p38 MAPK, without affecting their protein levels. The ERK1/2 activity is strongly suppressed, while the activity of p38 is increased. We have also found that the activity of upstream and specifi c for p38 MAPK kinase MEK3/6 is also stimulated by TBB. These original results clearly demonstrate the participation of CK2 in the signal transduction pathway controlling MEK3/6, p38 MAPK, and ERK1/2 in the used model system.

Role of the adapter protein SLP-76 in GPVI-dependent platelet procoagulant responses to collagen

Blood ◽  
2002 ◽  
Vol 100 (8) ◽  
pp. 2839-2844 ◽  
Author(s):  
Lorie Leo ◽  
Jorge Di Paola ◽  
Barbi A. Judd ◽  
Gary A. Koretzky ◽  
Steven R. Lentz
Keyword(s):  
Signal Transduction ◽  
Signal Transduction Pathway ◽  
Annexin V ◽  
Fold Increase ◽  
Surface Expression ◽  
Procoagulant Activity ◽  
Adapter Protein ◽  
Glycoprotein Vi ◽  
Granule Release

The adapter protein SLP-76 is a critical mediator of signal transduction via the platelet collagen receptor glycoprotein VI (GPVI) and its coreceptor FcRγ. We tested the hypothesis that SLP-76 is required for collagen-induced procoagulant responses in murine platelets. Platelets from SLP-76 null (SLP-76−/−) or heterozygous (SLP-76+/−) mice were activated with the GPVI agonist convulxin, and surface expression of P-selectin (a marker of granule release) and annexin V binding (a marker of procoagulant phospholipid) were determined by flow cytometry. Convulxin induced surface expression of P-selectin in SLP-76+/− platelets, but not SLP-76−/− platelets (P < .01), and failed to stimulate annexin V binding to either SLP-76+/−or SLP-76−/− platelets. Platelet procoagulant activity was measured in a prothrombinase assay. Convulxin did not stimulate procoagulant activity in either SLP-76+/− or SLP-76−/− platelets, but fibrillar collagen produced a 1.9-fold increase in procoagulant activity in both SLP-76+/− and SLP-76−/− platelets (P < .001 versus unstimulated platelets). Similar results were obtained with platelets from FcRγ null mice, for which collagen, but not convulxin, induced procoagulant activity (P < .01). Costimulation with thrombin and collagen produced a further (2.3-fold) increase in procoagulant activity in SLP-76+/− platelets (P < .05), but not in SLP-76−/− platelets. SLP-76−/− platelets also exhibited less annexin V binding than SLP-76+/−platelets after costimulation with thrombin and convulxin (P < .05). These findings demonstrate that an intact GPVI/FcRγ/SLP-76 signal transduction pathway is not essential for platelet procoagulant activity induced by collagen but is necessary for maximal procoagulant response to costimulation with thrombin plus collagen. Thus, both GPVI-dependent and GPVI-independent pathways contribute to collagen-induced platelet procoagulant activity.

scholarly journals MAPK Signal Transduction Pathway Regulation: A Novel Mechanism of Rat HSC-T6 Cell Apoptosis Induced by FUZHENGHUAYU Tablet

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Qi Wang ◽  
Hongbo Du ◽  
Min Li ◽  
Yue Li ◽  
Shunai Liu ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Target Genes ◽  
Stellate Cell ◽  
Signal Transduction Pathway ◽  
Differentially Expressed ◽  
Mrna Levels ◽  
Protein Levels ◽  
Control Serum ◽  
Pathway Regulation ◽  
Induced Apoptosis

FUZHENGHUAYU Tablets have been widely used in the treatment of liver fibrosis in China. Here, we investigate the apoptotic effect of FUZHENGHUAYU Tablet in rat liver stellate cell line HSC-T6. HSC-T6 cells were incubated with control serum or drug serum from rats fed with 0.9% NaCl or FUZHENGHUAYU Tablet, respectively. Cells exposed to drug serum showed higher proportions of early and late apoptotic cells than controls. The mRNA levels of collagens I and III, TGF-β1 andα-SMA were reduced by drug serum compared to control serum. Differentially expressed mRNAs and miRNAs were analyzed by microarray and sequencing, respectively. We identified 334 differentially expressed mRNAs and also 60 GOs and two pathways related to the mRNAs. Seventy-five differentially expressed miRNAs were down-regulated by drug serum and 1963 target genes were predicted. 134 GOs up-regulated in drug serum group were linked to miRNA targets, and drug serum also regulated 43 miRNA signal transduction pathways. Protein levels were evaluated by Western blot. Drug serum down-regulated (phospho-SAPK/JNK)/(SAPK/JNK) and up-regulated phospho-p38/p38 ratios. The study showed that FUZHENGHUAYU Tablet induced apoptosis in rat HSC-T6 cells possibly in part by activating p38 and inhibiting SAPK/JNK.

scholarly journals Enhancement of pertussis-toxin-sensitive Na+-dependent uridine transporter activity in HL-60 granulocytes by N-formylmethionyl-leucyl-phenylalanine

1993 ◽  
Vol 294 (3) ◽  
pp. 693-697 ◽  
Author(s):  
L B Goh ◽  
J A Sokoloski ◽  
A C Sartorelli ◽  
C W Lee
Keyword(s):  
Signal Transduction ◽  
Pertussis Toxin ◽  
Signal Transduction Pathway ◽  
Fold Increase ◽  
Ionophore A23187 ◽  
Transduction Pathway ◽  
Gradual Decline ◽  
Differentiated Cells ◽  
Dependent Transport ◽  
Full Activation

N-Formyl-Met-Leu-Phe (FMLP), at concentrations as low as 5 nM, caused an increase in intracellular uridine pools in dimethyl sulphoxide (Me2SO)-differentiated HL-60 cells. Intracellular uridine pools were elevated rapidly and reached a maximum within 10 min of exposure to 10 microM FMLP, followed by a gradual decline. This enhancement by FMLP was a consequence of a 3-fold increase in the Vmax of pertussis-toxin-sensitive Na(+)-dependent uridine transport system, with no change in the apparent Km. Km values of 2.67 +/- 0.45 and 3.85 +/- 0.52 microM and Vmax. values of 0.046 +/- 0.017 and 0.125 +/- 0.020 microM/s were obtained for untreated and FMLP-treated Me2SO-differentiated cells respectively. The effect of FMLP on the Na(+)-dependent transport of uridine in Me2SO-differentiated HL-60 cells was specific, as the facilitated transport of uridine was unaffected. Furthermore, this phenomenon was not observed in undifferentiated, phorbol 12-myristate 13-acetate (PMA)-differentiated or pertussis-toxin-treated Me2SO-differentiated HL-60 cells. Removal of extracellular Ca2+ with EGTA abolished the FMLP enhancement of uridine transport in a reversible manner, suggesting the involvement of Ca2+. However, the Ca2+ ionophore A23187 only partially mimicked the effect of FMLP. Similarly, with PMA the transport was sub-optimally enhanced, but a full activation was observed in cells treated with both A23187 and PMA. These findings suggest that activation of the Na(+)-dependent uridine transporter by FMLP in Me2SO-differentiated HL-60 cells involves a pertussis-toxin-sensitive G-protein with a bifurcating signal-transduction pathway.

scholarly journals Effect of TLR4/MyD88 Signaling Pathway on Expression of IL-1βand TNF-αin Synovial Fibroblasts from Temporomandibular Joint Exposed to Lipopolysaccharide

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Xuefen Lin ◽  
Jingjing Kong ◽  
Qingting Wu ◽  
Yingying Yang ◽  
Ping Ji
Keyword(s):  
Signal Transduction ◽  
Temporomandibular Joint ◽  
Interleukin 1 ◽  
Signal Transduction Pathway ◽  
Synovial Fibroblasts ◽  
Signal Pathways ◽  
Transduction Pathway ◽  
Inhibitory Peptide ◽  
Surface Receptors ◽  
Protein Levels

Accumulating evidence from previous studies suggested that interleukin-1 (IL-1β) and tumor necrosis factor-α(TNF-α) play an important role in pathogenesis of temporomandibular disorders (TMD). However, the cell surface receptors and the intracellular signal pathways leading to these cytokines expression are not fully understood. In the current study, we investigated the roles of Toll-like receptor 4 (TLR4) and its adaptor myeloid differentiation factor 88 (MyD88) in the expression of IL-1βand TNF-αin synovial fibroblasts (SFs) separated from rat temporomandibular joint (TMJ) with lipopolysaccharide (LPS) stimulation. The results showed that treatment with LPS could increase TLR4, MyD88, IL-1β, and TNF-αexpression at both mRNA and protein levels. In addition, increased expression of IL-1βand TNF-αcould be blocked by treatment with TAK-242, a blocker of TLR4 signaling, and also by MyD88 inhibitory peptide (MIP). These findings suggested that maybe TLR4/MyD88 signal transduction pathway participates in enhanced expression of IL-1 and TNF-αin patients with TMD. The activation of TLR4/MyD88 signal transduction pathway which results in production of proinflammatory factors may play a role in the pathogenesis of TMD.

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