Role of Allosteric:Zinc Interdomain Region of the Regulatory Subunit in the Allosteric Regulation of Aspartate Transcarbamoylase fromEscherichia coli

1998 ◽  
Vol 354 (2) ◽  
pp. 215-224
Author(s):  
Vipin K. Rastogi ◽  
Rosemarie Swanson ◽  
Yasha M. Hartberg ◽  
Melinda E. Wales ◽  
James R. Wild
Keyword(s):  
Allosteric Regulation ◽  
Aspartate Transcarbamoylase ◽  
Regulatory Subunit ◽  
Fromescherichia Coli

scholarly journals Role of Cys-295 on subunit interactions and allosteric regulation of phosphofructokinase-2 fromEscherichia coli

FEBS Letters ◽  
2005 ◽  
Vol 579 (11) ◽  
pp. 2313-2318 ◽  
Author(s):  
Andrés Caniuguir ◽  
Ricardo Cabrera ◽  
Mauricio Báez ◽  
Claudio C. Vásquez ◽  
Jorge Babul ◽  
...  
Keyword(s):  
Allosteric Regulation ◽  
Subunit Interactions ◽  
Fromescherichia Coli

scholarly journals PRKAR2A deficiency protects mice from experimental colitis by increasing IFN-stimulated gene expression and modulating the intestinal microbiota

2021 ◽  
Author(s):  
Lumin Wei ◽  
Rongjing Zhang ◽  
Jinzhao Zhang ◽  
Juanjuan Li ◽  
Deping Kong ◽  
...  
Keyword(s):  
Experimental Colitis ◽  
Regulatory Subunit ◽  
Protective Effects ◽  
Intestinal Epithelial ◽  
Catalytic Subunits ◽  
Regulatory Subunits ◽  
Pka Regulatory Subunit ◽  
Cross Fostering ◽  
Specific Deletion

AbstractProtein kinase A (PKA) plays an important role in regulating inflammation via its catalytic subunits. Recently, PKA regulatory subunits have been reported to directly modulate some signaling pathways and alleviate inflammation. However, the role of PKA regulatory subunits in colonic inflammation remains unclear. Therefore, we conducted this study to investigate the role of the PKA regulatory subunit PRKAR2A in colitis. We observed that PRKAR2A deficiency protected mice from dextran sulfate sodium (DSS)-induced experimental colitis. Our experiments revealed that the intestinal epithelial cell-specific deletion of Prkar2a contributed to this protection. Mechanistically, the loss of PRKAR2A in Prkar2a−/− mice resulted in an increased IFN-stimulated gene (ISG) expression and altered gut microbiota. Inhibition of ISGs partially reversed the protective effects against DSS-induced colitis in Prkar2a−/− mice. Antibiotic treatment and cross-fostering experiments demonstrated that the protection against DSS-induced colitis in Prkar2a−/− mice was largely dependent on the gut microflora. Altogether, our work demonstrates a previously unidentified function of PRKAR2A in promoting DSS-induced colitis.

Novel role of the protein phosphatase 1 regulatory subunit PPP1R3A in atrial fibrillation

2018 ◽  
Vol 124 ◽  
pp. 108
Author(s):  
Katherina Alsina ◽  
Mohit Hulsurkar ◽  
Chunxia Yao ◽  
Barbara Langer ◽  
David Chiang ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Protein Phosphatase ◽  
Protein Phosphatase 1 ◽  
Regulatory Subunit

scholarly journals Ref2, a regulatory subunit of the yeast protein phosphatase 1, is a novel component of cation homoeostasis

2010 ◽  
Vol 426 (3) ◽  
pp. 355-364 ◽  
Author(s):  
Jofre Ferrer-Dalmau ◽  
Asier González ◽  
Maria Platara ◽  
Clara Navarrete ◽  
José L. Martínez ◽  
...  
Keyword(s):  
Protein Phosphatase ◽  
Living Organism ◽  
Calcium Sensitivity ◽  
Growth Conditions ◽  
Protein Phosphatase 1 ◽  
Regulatory Subunit ◽  
Alkaline Ph ◽  
Yeast Protein ◽  
Increased Sensitivity

Maintenance of cation homoeostasis is a key process for any living organism. Specific mutations in Glc7, the essential catalytic subunit of yeast protein phosphatase 1, result in salt and alkaline pH sensitivity, suggesting a role for this protein in cation homoeostasis. We screened a collection of Glc7 regulatory subunit mutants for altered tolerance to diverse cations (sodium, lithium and calcium) and alkaline pH. Among 18 candidates, only deletion of REF2 (RNA end formation 2) yielded increased sensitivity to these conditions, as well as to diverse organic toxic cations. The Ref2F374A mutation, which renders it unable to bind Glc7, did not rescue the salt-related phenotypes of the ref2 strain, suggesting that Ref2 function in cation homoeostasis is mediated by Glc7. The ref2 deletion mutant displays a marked decrease in lithium efflux, which can be explained by the inability of these cells to fully induce the Na+-ATPase ENA1 gene. The effect of lack of Ref2 is additive to that of blockage of the calcineurin pathway and might disrupt multiple mechanisms controlling ENA1 expression. ref2 cells display a striking defect in vacuolar morphogenesis, which probably accounts for the increased calcium levels observed under standard growth conditions and the strong calcium sensitivity of this mutant. Remarkably, the evidence collected indicates that the role of Ref2 in cation homoeostasis may be unrelated to its previously identified function in the formation of mRNA via the APT (for associated with Pta1) complex.

Role of Rho kinases in PKG-mediated relaxation of pulmonary arteries of fetal lambs exposed to chronic high altitude hypoxia

2007 ◽  
Vol 292 (3) ◽  
pp. L678-L684 ◽  
Author(s):  
Yuansheng Gao ◽  
Ada D. Portugal ◽  
Sewite Negash ◽  
Weilin Zhou ◽  
Lawrence D. Longo ◽  
...  
Keyword(s):  
High Altitude ◽  
Chronic Hypoxia ◽  
Pulmonary Arteries ◽  
Regulatory Subunit ◽  
Fourth Generation ◽  
Minor Effect ◽  
Altitude Hypoxia ◽  
High Altitude Hypoxia ◽  
Rock Activity

An increase in Rho kinase (ROCK) activity is implicated in chronic hypoxia-induced pulmonary hypertension. In the present study, we determined the role of ROCKs in cGMP-dependent protein kinase (PKG)-mediated pulmonary vasodilation of fetal lambs exposed to chronic hypoxia. Fourth generation pulmonary arteries were isolated from near-term fetuses (∼140 days of gestation) delivered from ewes exposed to chronic high altitude hypoxia for ∼110 days and from control ewes. In vessels constricted to endothelin-1, 8-bromoguanosine-cGMP (8-Br-cGMP) caused a smaller relaxation in chronically hypoxic (CH) vessels compared with controls. Rp-8-Br-PET-cGMPS, a PKG inhibitor, attenuated relaxation to 8-Br-cGMP in control vessels to a greater extent than in CH vessels. Y-27632, a ROCK inhibitor, significantly potentiated 8-Br-cGMP-induced relaxation of CH vessels and had only a minor effect in control vessels. The expression of PKG was increased but was not accompanied with an increase in the activity of the enzyme in CH vessels. The expression of type II ROCK and activity of ROCKs were increased in CH vessels. The phosphorylation of threonine (Thr)696 and Thr850 of the regulatory subunit MYPT1 of myosin light chain phosphatase was inhibited by 8-Br-cGMP to a lesser extent in CH vessels than in controls. The difference was eliminated by Y-27632. These results suggest that chronic hypoxia in utero attenuates PKG-mediated relaxation in pulmonary arteries, partly due to inhibition of PKG activity and partly due to enhanced ROCK activity. Increased ROCK activity may inhibit PKG action through increased phosphorylation of MYPT1 at Thr696 and Thr850.

scholarly journals Circ_0000215 Exerts Oncogenic Function in Nasopharyngeal Carcinoma by Targeting miR-512-5p

2021 ◽  
Vol 9 ◽  
Author(s):  
Xinping Chen ◽  
Weihua Xu ◽  
Zhichao Ma ◽  
Juan Zhu ◽  
Junjie Hu ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Cell Lines ◽  
Cell Counting ◽  
Regulatory Subunit ◽  
Luciferase Reporter ◽  
Regulatory Function ◽  
Migration And Invasion ◽  
Circular Rnas

Background: Increasing circular RNAs (circRNAs) are reported to participate in cancer progression. Nonetheless, the role of circRNAs in nasopharyngeal carcinoma (NPC) has not been fully clarified. This work is aimed to probe the role of circ_0000215 in NPC.Methods: Circ_0000215 expression in NPC tissues and cell lines was examined by quantitative real-time polymerase chain reaction (qRT-PCR). Cell counting kit-8 (CCK-8) assay, 5-bromo-2′-deoxyuridine (BrdU) assay, scratch healing assay and Transwell experiment were executed to investigate the regulatory function of circ_0000215 on the proliferation, migration and invasion of NPC cells. RNA immunoprecipitation (RIP), pull-down and dual-luciferase reporter experiments were utilized to determine the binding relationship between circ_0000215 and miR-512-5p, and between miR-512-5p and phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) 3′UTR. The effects of circ_0000215 on NPC growth and metastasis in vivo were examined with nude mice model. Western blot was applied to detect the regulatory effects of circ_0000215 and miR-512-5p on PIK3R1 expression.Results: Circ_0000215 was overexpressed in NPC tissues and cell lines. The functional experiments confirmed that knockdown of circ_0000215 impeded the growth and metastasis of NPC cells in vitro and in vivo. Additionally, circ_0000215 could also work as a molecular sponge to repress miR-512-5p expression. PIK3R1 was validated as a target gene of miR-512-5p, and circ_0000215 could increase the expression level of PIK3R1 in NPC cells via suppressing miR-512-5p.Conclusion: Circ_0000215 is overexpressed in NPC and exerts oncogenic effects in NPC through regulating miR-512-5p/PIK3R1 axis.

Initiation and maintenance of NGF-stimulated neurite outgrowth requires activation of a phosphoinositide 3-kinase

1996 ◽  
Vol 109 (2) ◽  
pp. 289-300 ◽  
Author(s):  
T.R. Jackson ◽  
I.J. Blader ◽  
L.P. Hammonds-Odie ◽  
C.R. Burga ◽  
F. Cooke ◽  
...  
Keyword(s):  
Neurite Outgrowth ◽  
Pc12 Cells ◽  
Specific Inhibitor ◽  
Morphological Differentiation ◽  
Sympathetic Neuron ◽  
Neuronal Morphology ◽  
Regulatory Subunit ◽  
Membrane Reorganization ◽  
Phosphoinositide 3 Kinase

Application of nerve growth factor (NGF) to PC12 cells stimulates a programme of physiological changes leading to the development of a sympathetic neuron like phenotype, one aspect of which is the development of a neuronal morphology characterised by the outgrowth of neuritic processes. We have investigated the role of phosphoinositide 3-kinase in NGF-stimulated morphological differentiation through two approaches: firstly, preincubation with wortmannin, a reputedly specific inhibitor of phosphoinositide kinases, completely inhibited initial morphological responses to NGF, the formation of actin filament rich microspikes and subsequent neurite outgrowth. This correlated with wortmannin inhibition of NGF-stimulated phosphatidylinositol(3,4,5)trisphosphate (PtdInsP3) and phosphatidylinositol(3,4)bisphosphate (PtdIns(3,4)P2) production and with inhibition of NGF-stimulated phosphoinositide 3-kinase activity in anti-phosphotyrosine immunoprecipitates. Secondly, the overexpression of a mutant p85 regulatory subunit of the phosphoinositide 3-kinase, which cannot interact with the catalytic p110 subunit, also substantially inhibited the initiation of NGF-stimulated neurite outgrowth. In addition, we found that wortmannin caused a rapid collapse of more mature neurites formed following several days exposure of PC12 cells to NGF. These results indicate that NGF-stimulated neurite outgrowth requires the activity of a tyrosine kinase regulated PI3-kinase and suggest that the primary product of this enzyme, PtdInsP3, is a necessary second messenger for the cytoskeletal and membrane reorganization events which occur during neuronal differentiation.

scholarly journals The Role of Intersubunit Interactions for the Stabilization of the T State ofEscherichia coliAspartate Transcarbamoylase

2002 ◽  
Vol 277 (51) ◽  
pp. 49755-49760 ◽  
Author(s):  
Robin S. Chan ◽  
Jessica B. Sakash ◽  
Christine P. Macol ◽  
Jay M. West ◽  
Hiro Tsuruta ◽  
...  
Keyword(s):  
Small Angle ◽  
Structural State ◽  
Aspartate Transcarbamoylase ◽  
Wild Type ◽  
X Ray ◽  
X Ray Scattering ◽  
Intersubunit Interactions ◽  
T State ◽  
Ray Scattering

Homotropic cooperativity inEscherichia coliaspartate transcarbamoylase results from the substrate-induced transition from the T to the R state. These two alternate states are stabilized by a series of interdomain and intersubunit interactions. The salt link between Lys-143 of the regulatory chain and Asp-236 of the catalytic chain is only observed in the T state. When Asp-236 is replaced by alanine the resulting enzyme exhibits full activity, enhanced affinity for aspartate, no cooperativity, and no heterotropic interactions. These characteristics are consistent with an enzyme locked in the functional R state. Using small angle x-ray scattering, the structural consequences of the D236A mutant were characterized. The unliganded D236A holoenzyme appears to be in a new structural state that is neither T, R, nor a mixture of T and R states. The structure of the native D236A holoenzyme is similar to that previously reported for another mutant holoenzyme (E239Q) that also lacks intersubunit interactions. A hybrid version of aspartate transcarbamoylase in which one catalytic subunit was wild-type and the other had the D236A mutation was also investigated. The hybrid holoenzyme, with three of the six possible interactions involving Asp-236, exhibited homotropic cooperativity, and heterotropic interactions consistent with an enzyme with both T and R functional states. Small angle x-ray scattering analysis of the unligated hybrid indicated that the enzyme was in a new structural state more similar to the T than to the R state of the wild-type enzyme. These data suggest that three of the six intersubunit interactions involving D236A are sufficient to stabilize a T-like state of the enzyme and allow for an allosteric transition.

Sign in / Sign up

Export Citation Format

Share Document