scholarly journals Bone Morphogenic Protein (BMP) Signaling Up-regulates Neutral Sphingomyelinase 2 to Suppress Chondrocyte Maturation via the Akt Protein Signaling Pathway as a Negative Feedback Mechanism

2014 ◽  
Vol 289 (12) ◽  
pp. 8135-8150 ◽  
Author(s):  
Hironori Kakoi ◽  
Shingo Maeda ◽  
Naohiro Shinohara ◽  
Kanehiro Matsuyama ◽  
Katsuyuki Imamura ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Negative Feedback ◽  
Feedback Mechanism ◽  
Bone Morphogenic Protein ◽  
Bmp Signaling ◽  
Protein Signaling ◽  
Neutral Sphingomyelinase ◽  
Negative Feedback Mechanism ◽  
Chondrocyte Maturation

Flt3/ITD Enhances Hematopoietic Cell Migration Towards Chemokine CCL2 Independent of Blocking the Negative Feedback Mechanism on Rho-Associated Kinase

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3597-3597
Author(s):  
Seiji Fukuda ◽  
Chie Onishi ◽  
Tomohiro Hirade ◽  
Mariko Abe ◽  
Takeshi Taketani ◽  
...  
Keyword(s):  
Cell Migration ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Negative Feedback ◽  
Conflicts Of Interest ◽  
Feedback Mechanism ◽  
Hematopoietic Cell ◽  
Negative Feedback Mechanism ◽  
Chemokine Signaling ◽  
Qualitative Changes

Abstract Internal tandem duplication mutations in the Flt3 gene (Flt3/ITD) found in patients with AML is associated with extremely poor prognosis. Our previous report demonstrating Flt3/ITD-mediated enhancement of hematopoietic cell migration towards chemokine CXCL12 (SDF1) suggests that Flt3/ITD likely facilitates dissemination of AML cells in the patients. Following studies showed that CXCL12 transiently up-regulated the expression of Rho-associated kinase-1 (Rock1) but subsequently down-regulated Rock1 expression in the control cells, whereas this effect was abolished by Flt3/ITD. The results demonstrated that CXCL12 generates negative regulatory feedback on Rock1 expression to prevent excessive migration to CXCL12 in the control cells, whereas this mechanism is abrogated by Flt3/ITD, thereby inducing deregulated cell migration (Onishi et al. ASH 2012). However, it is not known if Flt3/ITD augments migration to other chemokines and whether Flt3/ITD-induced blockage of the negative feedback loop on Rock1 expression reflects a specific effect on CXCL12/CXCR4 signaling pathway or more global change by ITD-Flt3. We found that mRNA for CCR2, a receptor for chemokine CCL2, is expressed in human AML cells. Herein, we investigated the effect of Flt3/ITD on migration to CCL2 in hematopoietic cells. Expression of CCR2 was significantly higher in the M4 and M5 cases with AML compared to other FAB subtypes that are deposited in the public gene expression database. However, there was no difference in the mRNA level for CCR2 between Flt3/ITD+ and Flt3/ITDneg cases. Consistent with AML samples, expression of surface CCR2 protein in Ba/F3 cells transfected with Flt3/ITD is equivalent to the control cells lacking Flt3/ITD. While the control Flt3/ITDneg Ba/F3 cells failed to migrate towards 1, 5, 10 and 50ng/mL of CCL2, Flt3/ITD marginally but significantly enhanced the cell migration towards 5ng/mL of CCL2 in Ba/F3 cells within 4 hours compared to control. In the Flt3/ITDneg cells exposed to 5ng/mL of CCL2, the mRNA expression of Rock1 continued to increase without being down-regulated to the basal level within 4 hours, and did not show any biphasic changes. In the Flt3/ITD+ Ba/F3 cells, however, Rock1 expression was significantly elevated compared to Flt3/ITDneg cells prior to incubation with CCL2, but down-regulated to 50% of the original level by 5ng/mL of CCL2 within 30 minutes. In contrast, Rock1 expression was barely affected and remained elevated by CXCL12 in Flt3/ITD+ Ba/F3 cells. Elevated expression of CCR2 in the M4 and M5 AML suggests that CCR2 signaling pathways can regulate migration of AML cells with monocytic lineage. Similar to CXCL12, migration towards CCL2 was also enhanced by Flt3/ITD without up-regulating CCR2 expression, suggesting that the enhanced chemotaxis by Flt3/ITD is not specific to CXCL12 and likely attributed to qualitative changes in the CCL2/CCR2 signaling pathway rather than their quantitative increase. Down-regulation of Rock1 expression by CCL2 in Flt3/ITD+ Ba/F3 cells may represent one of the qualitative changes in the CCL2 signaling pathway. However, blocking the CXCL12-induced negative regulatory mechanism on Rock1 expression existing in the Flt3/ITD+ cells was not identified in the CCL2 signaling. These data indicate that while enhancement in cell migration to chemokines by Flt3/ITD is not specific to CXCL12, blocking the negative feedback mechanism on Rock1 expression is not necessarily used in other chemokine signaling pathways. Our data suggests that Flt3/ITD mutations regulate trafficking of AML cells by modulating various chemokine signaling, but divergent molecular mechanism is involved in regulating cell migration towards different chmeokines. Disclosures No relevant conflicts of interest to declare.

scholarly journals Rnf43

2017 ◽  
Vol 71 (1) ◽  
pp. 1-6 ◽  
Author(s):  
Stefano Serra ◽  
Runjan Chetty
Keyword(s):  
Tumor Suppressor ◽  
Signaling Pathway ◽  
Negative Feedback ◽  
Feedback Mechanism ◽  
Beta Catenin ◽  
Loss Of Function ◽  
Ring Type ◽  
Ubiquitin Protein Ligase ◽  
Negative Feedback Mechanism ◽  
Frequent Mutations

RNF43 (E3 ubiquitin-protein ligase RNF43 or RING-type E3 ubiquitin transferase RNF43) functions as a tumor suppressor, by exerting a predominant negative feedback mechanism in the Wnt/β-catenin signaling pathway. RNF43 inhibits Wnt/beta-catenin signaling by ubiquitinating Frizzled receptor and targeting it to the lysosomal pathway for degradation. Loss of function of RNF43 results in decrease/lack of degradation of Frizzled with enhancement of Wnt/β-catenin signaling pathway. Mutations of RNF43 have been reported in different cancers. We describe the structure of RNF43, its function and most frequent mutations in different cancers.

Activation of the Na+/K+-ATPase by insulin and glucose as a putative negative feedback mechanism in pancreatic beta-cells

2008 ◽  
Vol 457 (6) ◽  
pp. 1351-1360 ◽  
Author(s):  
M. Düfer ◽  
D. Haspel ◽  
P. Krippeit-Drews ◽  
L. Aguilar-Bryan ◽  
J. Bryan ◽  
...  
Keyword(s):  
Beta Cells ◽  
Negative Feedback ◽  
Pancreatic Beta Cells ◽  
Feedback Mechanism ◽  
Negative Feedback Mechanism

scholarly journals Negative feedback in ants: crowding results in less trail pheromone deposition

2013 ◽  
Vol 10 (81) ◽  
pp. 20121009 ◽  
Author(s):  
Tomer J. Czaczkes ◽  
Christoph Grüter ◽  
Francis L. W. Ratnieks
Keyword(s):  
Negative Feedback ◽  
Trail Pheromone ◽  
Distribution Networks ◽  
Feedback Mechanism ◽  
Lasius Niger ◽  
Feedback Signal ◽  
Control Mechanisms ◽  
Negative Feedback Mechanism ◽  
Self Organized ◽  
Fold Reduction

Crowding in human transport networks reduces efficiency. Efficiency can be increased by appropriate control mechanisms, which are often imposed externally. Ant colonies also have distribution networks to feeding sites outside the nest and can experience crowding. However, ants do not have external controllers or leaders. Here, we report a self-organized negative feedback mechanism, based on local information, which downregulates the production of recruitment signals in crowded parts of a network by Lasius niger ants. We controlled crowding by manipulating trail width and the number of ants on a trail, and observed a 5.6-fold reduction in the number of ants depositing trail pheromone from least to most crowded conditions. We also simulated crowding by placing glass beads covered in nest-mate cuticular hydrocarbons on the trail. After 10 bead encounters over 20 cm, forager ants were 45 per cent less likely to deposit pheromone. The mechanism of negative feedback reported here is unusual in that it acts by downregulating the production of a positive feedback signal, rather than by direct inhibition or the production of an inhibitory signal.

scholarly journals RGS4 is a negative feedback mechanism of Angiotensin II‐mediated aldosterone production in human adrenal cells

2006 ◽  
Vol 20 (4) ◽  
Author(s):  
Damian G Romero ◽  
Maria W Plonczynski ◽  
Licy L Yanes ◽  
Tanganika R Washington ◽  
Gina Covington ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Negative Feedback ◽  
Feedback Mechanism ◽  
Adrenal Cells ◽  
Negative Feedback Mechanism ◽  
Aldosterone Production

Effect of Tumor Growth Factor-β on Osteogenesis in Osteoporosis Rats by Regulating Bone Morphogenetic Protein Signaling Pathway

2020 ◽  
Vol 10 (12) ◽  
pp. 1884-1890
Author(s):  
Jing Tian ◽  
Qianying Zhao ◽  
Dapeng Zhou ◽  
Bing Xie
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Bmp Signaling ◽  
Control Group ◽  
Protein Signaling ◽  
Alp Activity ◽  
Tissue Repair And Regeneration ◽  
Tumor Growth Factor ◽  
Morphogenetic Protein ◽  
Proliferation And Differentiation

The balance of osteoblasts and osteoclasts is critical for bone formation and remodeling and imbalance causes osteoporosis (OP). TGF-β regulates bone tissue repair and regeneration, but TGF-β’s role in osteogenesis in OP has not been elucidated. OVX-induced OP rat models were constructed and rat BMSCs were isolated and assigned into control group, OP group, and TGF-β group (transfected with TGF-β1 plasmid followed by analysis of cell proliferation by MTT assay, RUNX2 and OPN expression by Real time PCR, ALP activity and secretion of TGF-β, BMP-2 and BMP-9 by ELISA. In addition, RANKL was added to induce BMSCs differentiation into to osteoclasts which were transfected with TGF-β1 followed by analysis of cell proliferation, c-Fos and TRAP expression and secretion of BMP-2 and BMP-9. OP group rats had significantly reduced secretion of TGF-β1, BMP-2 and BMP-9, reduced cell proliferation, decreased RUNX2 and OPN expression and ALP activity (P <0.05). Transfection of TGF-β1 in BMSCs of OP group rats could significantly reverse the above changes (P <0.05). TGF-β1 significantly inhibited osteoclast proliferation, decreased expression of c-Fos and TRAP, and increased secretion of BMP-2 and BMP-9 (P <0.05). TGF-β1 level in OP is decreased. Up-regulating TGF-β promotes osteoblast differentiation in OP rats by regulating BMP signaling pathway, and inhibits osteoclast proliferation and differentiation.

Intrinsic and extrinsic mechanisms contribute to maintain the JAK/STAT pathway aberrantly activated in T-type large granular lymphocyte leukemia

Blood ◽  
2013 ◽  
Vol 121 (19) ◽  
pp. 3843-3854 ◽  
Author(s):  
Antonella Teramo ◽  
Cristina Gattazzo ◽  
Francesca Passeri ◽  
Albana Lico ◽  
Giulia Tasca ◽  
...  
Keyword(s):  
Negative Feedback ◽  
Feedback Mechanism ◽  
Large Granular Lymphocyte ◽  
Large Granular Lymphocyte Leukemia ◽  
Negative Feedback Mechanism ◽  
Key Points ◽  
Stat Pathway

Key PointsIn T-LGLL, autologous LGL-depleted PBMCs release high levels of IL-6 contributing to the constitutive STAT3 activation in leukemic LGL. Leukemic LGLs show SOCS3 down-modulation, which is responsible for lack of the negative feedback mechanism controlling STAT3 activation.

Association of rs12997 variant in the ACVR1 gene: a member of bone morphogenic protein signaling pathway with primary open-angle glaucoma in a Saudi cohort

2020 ◽  
pp. jim-2020-001596
Author(s):  
Altaf A Kondkar ◽  
Taif A Azad ◽  
Tahira Sultan ◽  
Essam A Osman ◽  
Faisal A Almobarak ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Primary Open Angle Glaucoma ◽  
Open Angle Glaucoma ◽  
Large Population ◽  
Bone Morphogenic Protein ◽  
Additive Models ◽  
Type I ◽  
Protein Signaling ◽  
Open Angle ◽  
Retrospective Case

We investigated the association between variants rs12997 in activin A receptor type I (ACVR1) and rs1043784 in BMP6 located in the 3' untranslated region, and primary open-angle glaucoma (POAG). The retrospective case-control study used TaqMan real-time PCR assay to genotype 400 subjects, including 150 patients with POAG and 250 controls. The minor ‘G’ allele of rs12997 in ACVR1 showed significant association with POAG (p=0.027, OR=1.39, 95% CI=1.03 to 1.87). Likewise, rs12997 genotypes showed moderate association with POAG in recessive (p=0.048, OR=1.80, 95% CI=1.01 to 3.20) and log-additive models (p=0.030, OR=1.39, 95% CI=1.03 to 1.87), but did not survive Bonferroni correction. Rs1043784 in BMP6 showed no associations. Furthermore, rs12997 G/G genotype significantly (p=0.033) increased the risk of POAG (twofolds) independent of age, sex and rs1043784 genotypes in regression analysis. However, clinical variables such as intraocular pressure and cup/disc ratio showed no association with both the polymorphisms. To conclude, the study shows a modest association between rs12997 in the ACVR1 gene, a member of the bone morphogenic protein signaling pathway and POAG. However, the results need further replication in large population-based cohorts and different ethnicities to validate its role as an important genetic biomarker.

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