25 results on '"A.A. Aleksandrov"'
Search Results
2. Analytical Study of Heat Transfer When Heating or Cooling a Limited Volume of Liquid
- Author
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A.A. Aleksandrov, V.A. Akatev, M.P. Tyurin, E.S. Borodina, and O.I. Sedlyarov
- Subjects
General Computer Science ,General Mathematics ,General Engineering ,General Physics and Astronomy ,General Chemistry - Abstract
The paper shows the results of analytical studies of heat transfer when heating or cooling a limited volume of liquid. The purpose of the research was to determine the size of the heat transfer surface, with the initial parameters of the coolants, the final temperature in the reactor and its thermal equivalent, as well as the flow rate of the second coolant through the heat exchanger corresponding to the water equivalent at a given cooling time τo. Moreover, if intensive mixing is carried out in the vessel, i.e., if the temperature of the second heat carrier practically does not change along the length of the heat transfer surface, then W2 → ∞. The solution was based on the Laplace --- Carson integral transform. The exact solution was converted for special cases of heat transfer. In particular, it should be noted that in many practical cases formulas give a fairly good approximation to the exact solution. Only at low values of the heat transfer coefficient, as well as when the volume occupied by the coolant inside the heat exchanger is commensurate with the volume of the liquid contained in the vessel, it is necessary to apply the given exact solution
- Published
- 2021
3. OPTIMIZATION OF THE OPTION SELECTED FOR THE IMPLEMENTATION OF THE DEVELOPMENT AND PROGRAM FOR ADDITIONAL EXPLORATION OF THE TURONIAN DEPOSIT, TAKING INTO ACCOUNT THE INFLUENCE OF GEOLOGICAL AND TECHNOLOGICAL UNCERTAINTIES
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O.V. Novopashin, A.A. Aleksandrov, A.N. Kiselev, I.S. Degtyarev, Kharampurneftegaz Llc, D.D. Romanova, and R.A. Yagudin
- Subjects
Development (topology) ,Geology ,Construction engineering - Published
- 2021
4. FINDING DEFECTS IN AUTOMATIC CONTROL SYSTEMS BASED ON STRUCTURE SENSITIVITY FUNCTIONS AND ANALYSIS OF INTEGRAL ESTIMATES OF OUTPUT SIGNALS
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A.A. Aleksandrov, S.S. Shalobanov, and S.V. Shalobanov
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Automatic control ,Computer science ,Control theory ,Structure (category theory) ,Sensitivity (control systems) - Abstract
The paper presents an algorithm for defects screening in a continuous dynamic system with a depth of up to dynamic block based on the structure sensitivity function and the sign analysis of integral esti-mates of the output signals deviations.
- Published
- 2021
5. Improving the quality of predicted technological parameters of development by using integrated approach to modeling
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E.O. Tolkacheva, O.A. Loznuk, A.A. Khakimov, Kharampurneftegas Llc, Rf, Tyumen, A.A. Aleksandrov, R.A. Yagudin, and Yu.D. Kholkina
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Fuel Technology ,Computer science ,media_common.quotation_subject ,Energy Engineering and Power Technology ,Quality (business) ,Integrated approach ,Manufacturing engineering ,media_common - Published
- 2021
6. Characteristics of rocket fuel cooling by means of liquid nitrogen in ground complex tanks equipped with heat exchange jackets
- Author
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A.A. Aleksandrov, I.V. Barmin, K.I. Denisova, A.V. Zolin, S.K. Pavlov, and V.V. Chugunkov
- Abstract
The authors developed dedicated computational techniques and combined those with numerical simulation of heat transfer processes in ground complex tanks equipped with heat exchange jackets to discover the specifics of how rocket fuel may be cooled with liquid nitrogen used to sparge antifreeze in the cavities of the heat exchange jackets. The paper provides estimation data for rocket fuel cooling efficiency as a function of mass flow rate of liquid nitrogen for various options of setting up fuel mixing in the storage tank during cooling.
- Published
- 2022
7. Analytical Study of Nonstationary Modes in Recuperative Heat Exchangers
- Author
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E. S. Borodina, M. P. Tyurin, A.A. Aleksandrov, O. I. Sedlyarov, and Vladimir Akatev
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010407 polymers ,Materials science ,General Computer Science ,General Mathematics ,General Engineering ,General Physics and Astronomy ,02 engineering and technology ,General Chemistry ,Mechanics ,01 natural sciences ,0104 chemical sciences ,020401 chemical engineering ,Heat exchanger ,0204 chemical engineering - Abstract
Recuperative heat exchanger transient operation modes during the start-up were considered in order to identify the time for establishing the stationary mode. This is important in carrying out technological processes that require constancy in values of certain parameters ensuring both product quality and process safety. The research was carried out using the analytical method for direct-flow and counter-flow heat exchangers. It was demonstrated that stationary state establishment in the direct-flow heat exchangers occurs immediately after the heat carrier gets into the apparatus. It should be noted that the entire apparatus reaches the stationary mode, when the slower heat carrier arrives at the apparatus output section. In case of a heat exchanger with the heat carrier counter-flow, it was found out that at the moment of the less heated heat carrier appearing at the apparatus output section, it was having the highest temperature. Then the temperature was decreasing, and after passing its minimum was beginning to oscillate along a curve with the damping amplitude. In the case under consideration, the stationary process started, when the dimensionless time value was ϕ ≥ 0.5. The indicated solution was obtained under assumption that thermal and physical characteristics were constant in time and space. It was assumed that total heat capacity of the heat exchanger heat transferring wall was infinitesimal. This assumption is valid with an error of up to 1 % at Fo ≥ 100, which is the case in most practical cases. For apparatuses under study, a formula was also obtained for the time required to reach the stationary state
- Published
- 2020
8. Development of a Design Algorithm for the Logistics System of Product Distribution of the Mechanical Engineering Enterprise
- Author
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N.V. Kunkov, A.S. Vodchits, D.G. Lyakhovich, I.N. Omelchenko, and A.A. Aleksandrov
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Development (topology) ,Computer science ,0211 other engineering and technologies ,021108 energy ,02 engineering and technology ,Manufacturing engineering ,Product distribution ,021106 design practice & management - Abstract
The purpose of this research is to represent the results of the development of the design algorithm for the logistics system for the distribution of products of a mechanical engineering enterprise, which would determine the characteristics of the production distribution channel, the optimal arrangement of the elements of the logistics system of product distribution in the environment, and also to optimize the resources flow with regard to the limitations. The main content of this research is the analysis of publications of Russian and foreign scientists and specialists in the field of production management, modeling and optimization of organizational structures and production processes, design of logistics systems. The practical significance of the research is the possibility of the appliance of the presented algorithm by the management team of a mechanical engineering enterprise in a market environment. It would permit to improve the efficiency of using the existing resources of the enterprise. This article is addressed to specialists in the field of theory and practice of production organization
- Published
- 2020
9. Numerical Investigation of Fluid Flow between Rotating Permeable Cylindrical Surfaces
- Author
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Vladimir Devisilov, E. Yu. Sharai, and A.A. Aleksandrov
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Materials science ,General Computer Science ,General Mathematics ,General Engineering ,General Physics and Astronomy ,02 engineering and technology ,General Chemistry ,Mechanics ,021001 nanoscience & nanotechnology ,01 natural sciences ,010305 fluids & plasmas ,0103 physical sciences ,Fluid dynamics ,0210 nano-technology - Abstract
The paper presents numerical simulation results concerning fluid flow in the annular channel of a hydrodynamic filter comprising a perforated protective screen located between another perforated protective screen and a filtering screen, both cylindrical. We investigated the effects of the following two parameters on the flow structure: the perforated area of the protective screen and the width of the annular channel between the protective and filtering cylindrical screens. We established that increasing the annular channel width and the perforation area of the protective screen leads to secondary vortex structures forming in the channel. We obtained circumferential velocity distribution in the channel formed by the protective and filtering screens of the hydrodynamic filter. We show that, in the bracket of modal and design parameters under consideration, a power curve with an exponent in the 2.4--3.3 range may be used to approximate the circumferential velocity profile. We discovered that the structural and modal parameters of the channel between the rotating permeable cylindrical surfaces control the intensity of the deterministic separation process components. Channel width and perforation area are structural parameters; angular velocity is a modal parameter. Arranging the flow in a hydrodynamic filter in the way proposed makes it possible to decrease the intensity of random separation process components in multi-phase media.
- Published
- 2020
10. Investigation of the Nonstationary Energy Distribution of an Atomic Collision Cascade
- Author
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E.Yu. Baryscheva, E.V. Metelkin, V.A. Akatev, and A.A. Aleksandrov
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Physics ,Energy distribution ,General Computer Science ,020209 energy ,General Mathematics ,05 social sciences ,General Engineering ,General Physics and Astronomy ,02 engineering and technology ,General Chemistry ,Collision ,Computational physics ,Kinetic equations ,0502 economics and business ,0202 electrical engineering, electronic engineering, information engineering ,Collision cascade ,050207 economics - Abstract
In this paper, we derive a nonstationary distribution function describing the energy distribution of the cascade of moving atoms taking into account their multiplication. The function was derived by solving the Boltzmann kinetic equation. The development of the cascade was considered for the materials consisting of atoms of the same type without taking into account the binding energy of atoms at the crystal lattice sites. The scattering of moving atoms is assumed to be elastic and spherically symmetrical in a center-of-inertia system, and the interaction cross-section is assumed to be constant. The use of these assumptions allows us to derive simple analytic formulas for the nonstationary energy distribution function for the cascade and analyze its main distinctive features. The results obtained allow evaluating the accuracy of various approximate solutions.
- Published
- 2019
11. PUBLIC WARNING AS A BASIS FOR PROTECTION IN EMERGENCY SITUATIONS OF THE TECHNOGENOUS CHARACTER
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A. G. Gumerov, G. A. Sharipov, P. S. Khafizov, Kozlowski Waldemar, and A.A. Aleksandrov
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Character (mathematics) ,Basis (linear algebra) ,Computer science ,Computer security ,computer.software_genre ,computer ,Emergency situations - Published
- 2019
12. Investigation Heat Transfer Parameters for a Helical-Coil Heat Exchanger in a Two-Phase Medium
- Author
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S.K. Pavlov, A.A. Aleksandrov, V.V. Chugunkov, and I.V. Barmin
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Materials science ,General Computer Science ,General Mathematics ,0211 other engineering and technologies ,General Engineering ,General Physics and Astronomy ,Thermodynamics ,02 engineering and technology ,General Chemistry ,020303 mechanical engineering & transports ,0203 mechanical engineering ,Phase (matter) ,Heat transfer ,Heat exchanger ,021108 energy ,Helical coil - Abstract
The paper focuses on hydrocarbon fuel cooling in launch vehicles, specifically considering experimental technique and results obtained during investigation of one of the primary heat exchanger parameters, that is, heat transfer coefficient of the heat exchanger surface. We present a model of efficient hydrocarbon fuel cooling by means of intensifying heat transfer on the external heat exchanger surface due to nitrogen sparging causing active motion in the liquid heat carrier. We obtained quantitative data regarding heat transfer on the external surface of a helical-coil heat exchanger located in a two-phase medium consisting of antifreeze and nitrogen, in the temperature range of 243--293 K. We derived a similarity equation for calculating heat transfer coefficient on the external heat exchanger surface, which is required to determine the heat exchanger surface area and to compute heat transfer from hydrocarbon fuel to the two-phase medium consisting of antifreeze and nitroge.
- Published
- 2019
13. Solubility of oxygen in Fe-Co system melts containing hafnium
- Author
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V.Ya. Dashevskiy and A.A. Aleksandrov
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chemistry ,Inorganic chemistry ,chemistry.chemical_element ,Solubility ,Oxygen ,Hafnium - Published
- 2019
14. Develop a Model to Study the Energy Distribution of Cascades of Atomic Collisions
- Author
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V.A. Akatev, A.A. Aleksandrov, E.Yu. Baryscheva, and E.V. Metelkin
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Nuclear physics ,Physics ,Energy distribution ,General Computer Science ,General Mathematics ,General Engineering ,General Physics and Astronomy ,General Chemistry ,Atomic collisions - Abstract
In this paper, based on the solution of the Boltzmann kinetic equation, we determine the energy distribution function describing the steady-state deceleration of the cascade of moving atoms taking into account their multiplication at the power interaction potential U∼1/rn.A new approach to the solution of the kinetic equation based on the extended concept of primary knocked-on atoms (PKA) is used for its calculation. One of the advantages of using the power interaction potential is that in this case it is possible to obtain simple analytical formulas for the distribution function of the cascade of slowing-down atoms taking into account their multiplication and demonstrate the simplicity and convenience of the proposed new approach to the solution of the kinetic equation. On the other hand, based on the obtained results it is possible to estimate the accuracy of various approximate solutions. It is shown that this approach will be applicable to other interatomic interaction potentials, if the average PKA energy loss in individual collisions decreases monotonically with decreasing energy, and the relative PKA energy loss in individual collisions will be small.
- Published
- 2019
15. Indicators of efficiency of liquid nitrogen fuel cooling in tanks with integrated heat exchangers
- Author
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A.A. Aleksandrov, I.V. Barmin, K.I. Denisova, and V.V. Chugunkov
- Subjects
020301 aerospace & aeronautics ,020303 mechanical engineering & transports ,0203 mechanical engineering ,02 engineering and technology - Abstract
The paper describes the fuel cooling system which uses liquid nitrogen in the tanks of ground complexes equipped with integrated heat exchangers. We analyzed the characteristics of cooling liquid fuel in tanks with integrated heat exchangers filled with antifreeze, when sparging antifreeze with liquid nitrogen. As a result of the analysis, we introduced the indicators to assess the efficiency of the considered technical solutions in comparison with the existing options for constructing these systems. Furthermore, we developed a mathematical model of the cooling process in the form of a system of equations for temporary changes in the temperature of antifreeze and fuel, including the changes at various modes of fuel mixing. The paper gives the results of studies carried out in order to increase the efficiency of fuel cooling processes at various flow rates of liquid nitrogen by organizing the processes of its heat exchange with the surfaces of the integrated heat exchanger and the use of various types of antifreeze.
- Published
- 2021
16. Engineering personnel - the future of the innovative economy of the country
- Author
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A.A. Aleksandrov, V.K. Baltyan, A.S. Petrakov, and V.G. Fedorov
- Published
- 2021
17. Analysis of the efficiency of hydrocarbon propellant cooling using liquid nitrogen and a combination of recuperative heat exchangers
- Author
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A.A. Aleksandrov, A.V. Zolin, I.V. Barmin, and V.V. Chugunkov
- Subjects
Propellant ,chemistry.chemical_classification ,animal structures ,Materials science ,musculoskeletal, neural, and ocular physiology ,technology, industry, and agriculture ,macromolecular substances ,02 engineering and technology ,Liquid nitrogen ,01 natural sciences ,010305 fluids & plasmas ,020303 mechanical engineering & transports ,Hydrocarbon ,0203 mechanical engineering ,Chemical engineering ,chemistry ,0103 physical sciences ,Heat exchanger - Abstract
The paper describes the propellant cooling system using liquid nitrogen and a combination of recuperative heat exchangers, including sections of the double pipe heat exchanger and a twisted heat exchanger located in a tank with antifreeze, cooled by nitrogen gas coming out of the sections of the double pipe heat exchanger. Mathematical models of cooling processes for two variants of movement of propellant and liquid nitrogen in the channels of the double pipe heat exchanger sections are considered. Their using makes it possible to analyze the efficiency of propellant cooling operations depending on its mass, design parameters of the system tanks and heat exchangers, consumption characteristics of nitrogen and propellant, as well as to predict the required mass of liquid nitrogen and the time of propellant cooling during the operation of launching complex propellant-feed systems. Calculated dependences and simulation results of propellant and antifreeze cooling in a tank with a twisted heat exchanger are presented. The influence of variants of arranging propellant cooling processes and liquid nitrogen consumption on the efficiency of the cooling system is analyzed. Comparing to the available systems the capability of reducing the cost of liquid nitrogen are identified as well as reducing time of the propellant cooling operations by means of equipping launch complexes.
- Published
- 2020
18. MODERN METHODS FOR THE SELECTION OF EFFECTIVE DEMULGATORS FOR OIL DEHYDRATION IN EASTERN SIBERIA
- Author
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N.V. Bryzhevatykh, M.V. Semykin, E.V. Shakirova, and A.A. Aleksandrov
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business.product_category ,Petroleum engineering ,Sedimentation (water treatment) ,Mixing (process engineering) ,medicine.disease ,Demulsifier ,Desalination ,Volume (thermodynamics) ,Emulsion ,Bottle ,medicine ,Environmental science ,Dehydration ,business - Abstract
Background Oilfield preparation of hydrocarbons is one of the most urgent tasks in the development of oil fields. The depth of dehydration and desalination of oil significantly depends on the temperature of the emulsion, the process of interaction of the demulsifier and the result of their mixing. Aims and Objectives The aim of the work is to conduct experiments on the selection of demulsifiers for oils of Eastern Siberia. The research involved oils from the Danilovskoye and Ichedinskoye fields and demulsifiers: SNPKh 4802, DIN 4E. Metods Using sedimentation in cylinders (Bottle test), the indicators of the dehydration process of oil-water emulsions were analyzed. To maintain the temperature regime, the obtained oil-water emulsions were poured into cylinders with a volume of 100 ml and placed in a thermostat. Every 15 min, readings were recorded for the amount of settled water. The investigated physical and chemical parameters of demulsifiers contributed to the identification of the most effective for each field. The experiments were continued on the Lumifuge instrument, where the results were confirmed. The obtained graphs of the Danilovskaya and Ichyodinskaya emulsions with the addition of demulsifiers indicate that the separation of water has occurred and two phases have formed: oil - water. Results An analysis of the effect of demulsifiers on dehydration processes using the example of oils from Eastern Siberia showed that with the addition of a demulsifier, the completion time of the process is reduced by 2 times, and almost complete separation of water is observed. The choice of the optimal parameters of the demulsification process of the studied oils is substantiated: the consumption of the demulsifier, the temperature, the intensity of mixing.
- Published
- 2021
19. Optic nerve head microcirculation and morphometry in normal-tension glaucoma
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R.R. Sattarova, G.R. Ismagilova, A.Sh. Zagidullina, B. M. Aznabaev, and A.A. Aleksandrov
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Ophthalmology ,medicine.medical_specialty ,business.industry ,Normal tension glaucoma ,Optic nerve ,Medicine ,Head (vessel) ,business ,Microcirculation - Published
- 2017
20. Tsunami Consequences Modelling and Risk Assessment by using GIS-Technologies
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V.I. Larionov, S.P. Sushchev, and A.A. Aleksandrov
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Environmental science ,Risk assessment ,Environmental planning - Published
- 2018
21. METHODOLOGICAL FEATURES OF RISK ASSESSMENT FOR POPULATION AND TERRITORIES IN ACCIDENTS WITH HAZARDOUS CHEMICALS RELEASE
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A.A. Aleksandrov, V.I. Larionov, and S.P. Sushchev
- Published
- 2021
22. Mathematical Software For Evaluating And Supporting The Selection Decision On Academic Programs
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A.N. Lazareva, Alexandra A. Zakharova, and A.A. Aleksandrov
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Knowledge management ,business.industry ,Order (exchange) ,Computer science ,Mathematical software ,Fuzzy set ,Information system ,Selection (linguistics) ,Information support ,business ,Educational institution ,Academic program - Abstract
The article explains the importance of developing methods and tools in order to provide information support when selection decisions on academic programs are made by individuals. We have developed a model for integrated evaluation of academic programs in view of aims students want to attain and competencies to acquire when entering the profession and building individual careers. The proposed information system provides information interaction among stakeholders and main actors involved in the education market: individuals (prospective students) and educational institutions. Keywords—individuals, educational institution, academic program, integrated evaluation, fuzzy set, alternatives, information system.
- Published
- 2016
23. CFTR is a Monomer: Biochemical and Functional Evidence
- Author
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Xiu-Bao Chang, A.A. Aleksandrov, J.R. Riordan, and Jey-Hsin Chen
- Subjects
congenital, hereditary, and neonatal diseases and abnormalities ,Physiology ,Immunoprecipitation ,Lipid Bilayers ,Biophysics ,Cystic Fibrosis Transmembrane Conductance Regulator ,Gene Expression ,Kidney ,Affinity binding ,Cystic fibrosis ,Membrane Potentials ,Epitopes ,chemistry.chemical_compound ,Species Specificity ,Chloride Channels ,Cricetinae ,Microsomes ,medicine ,Animals ,Humans ,Protein Structure, Quaternary ,Secretory pathway ,Chemistry ,Endoplasmic reticulum ,Cell Biology ,respiratory system ,medicine.disease ,Recombinant Proteins ,digestive system diseases ,respiratory tract diseases ,Cell biology ,Monomer ,Chloride channel ,Protein quaternary structure - Abstract
Although the CFTR protein alone is sufficient to generate a regulated chloride channel, it is unknown how many of the polypeptides form the channel. Using biochemical and functional assays, we demonstrate that the CFTR polypeptide is a monomer. CFTR sediments as a monomer in a linear, continuous sucrose gradient. Cells co-expressing different epitope-tagged CFTR provide no evidence of co-assembly in immunoprecipitation and nickel affinity binding experiments. Co-expressed wild-type and DF508 CFTR are without influence on each other in their ability to progress through the secretory pathway, suggesting they do not associate in the endoplasmic reticulum. No hybrid conducting single channels are seen in planar lipid bilayers with which membrane vesicles from cells co-expressing similar amounts of two different CFTR conduction species have been fused.
- Published
- 2002
24. The 4π-fragment-spectrometer FOBOS
- Author
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V.V. Trofimov, S.V. Radnev, S. Dshemuchadse, W.D. Fromm, W. von Oertzen, L. Dietterle, G. Renz, R. Yanez, M. Wilpert, M. Andrassy, Yu. Ts. Oganessian, Sh. Heinitz, V.E. Zhuchko, P. Gippner, C. Umlauf, E. Will, A.A. Aleksandrov, I.V. Kolesov, V.N. Doronin, V.G. Tishchenko, K. Heidel, Yu. E. Penionzhkevich, W. Seidel, D.V. Vakatov, L.A. Rubinskaya, W. Wagner, M. Danziger, Yu.V. Pyatkov, S.A. Ivanovsky, D. May, A.P. Sirotin, G. Pausch, V.A. Vitenko, H.-G. Ortlepp, D.I. Shishkin, I.A. Aleksandrova, O.V. Strekalovsky, M. Gebhardt, I.P. Tsurin, H. Sodan, I.D. Sandrev, D.V. Kamanin, V.M. Vasko, H. Homeyer, C.-M. Herbach, L. Zrodlowski, P. Ziem, B. Czech, A. Budzanowski, S.I. Merzlyakov, A. S. Fomichev, K.D. Schilling, and A. Matthies
- Subjects
Nuclear reaction ,Physics ,Nuclear and High Energy Physics ,Scintillation ,Spectrometer ,Physics::Instrumentation and Detectors ,Nuclear Theory ,Detector ,Nuclear physics ,Fragmentation (mass spectrometry) ,Ionization ,Nuclear Experiment ,Spectroscopy ,Instrumentation ,Spontaneous fission - Abstract
The 4π-fragment-spectrometer FOBOS developed for heavy-ion research at beam energies of 10–100 AMeV has been commissioned for physical experiments at the Flerov Laboratory of Nuclear Reactions of the Joint Institute for Nuclear Research in Dubna. Based on the logarithmic detector principle, it is able to register charged fragments from protons up to heavy residual nuclei in a large dynamical range. Position-sensitive avalanche counters, axial ionization chambers and CsI(Tl) scintillation detectors are arranged in three concentric detector shells. An array of phoswich detectors is used as a more granular forward detector at narrow polar angles. The modular concept of FOBOS allows for different experimental application in the field of exclusive fragment spectroscopy at medium multiplicities. For illustration, the fragment spectroscopy studies concerning the spontaneous fission process and the fragmentation of hot nuclei by means of the FOBOS set-up are considered.
- Published
- 1998
25. Influence of phosphorylation by protein kinase A on CFTR at the cell surface and endoplasmic reticulum
- Author
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John W. Hanrahan, F.S. Seibert, David M. Clarke, Xiu-Bao Chang, A.A. Aleksandrov, and John R. Riordan
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Protein Conformation ,Phosphatase ,Biophysics ,Cystic Fibrosis Transmembrane Conductance Regulator ,Endoplasmic Reticulum ,Biochemistry ,Exocytosis ,Cystic fibrosis ,Cell membrane ,Protein kinase A ,medicine ,Phosphoprotein Phosphatases ,Animals ,Humans ,Amino Acid Sequence ,CFTR ,Phosphorylation ,Binding Sites ,Kinase ,Chemistry ,Endoplasmic reticulum ,Cell Membrane ,Cell Biology ,Cyclic AMP-Dependent Protein Kinases ,Cell biology ,Enzyme Activation ,medicine.anatomical_structure ,Chloride channel ,Ion Channel Gating - Abstract
CFTR possesses a large cluster of strict dibasic consensus sites for phosphorylation by protein kinase A (PKA) in the R-domain and an obligatory dependence on phosphorylation is a hallmark of CFTR Cl(-) channel function. Removal of as many as 11 of these sites reduces the conformational change in the R-domain and the degree of channel activation in response to PKA. However, until recently a completely PKA-unresponsive CFTR variant has not been reported, leaving open the possibility that the residual response may be mediated by associating ancillary phosphoproteins. We traced the residual PKA-catalyzed (32)P-labelling of the variant with 11 sites mutagenized (11SA) to distinct CNBr phosphopeptides within the R-domain. Mutagenesis of 4 additional monobasic sites in these segments produced a 15SA variant in which Cl(-) channel response to PKA was abolished. Therefore, it can be concluded that ancillary phosphoproteins do not contribute to CFTR activation by PKA. Notably, however, the 15SA protein did exhibit a low level of constitutive channel activity not dependent on PKA, which might have reflected a down-regulating effect of phosphorylation of one or two of the 15 sites as suggested by others. However, this did not prove to be the case.Since immature CFTR has been claimed to be active in the endoplasmic reticulum (ER), we also examined whether it can be phosphorylated in cells and what influence if any this might have on its susceptibility to degradation. Teleologically, activation by phosphorylation of CFTR Cl(-) channels in the ER might be undesirable to the cell. Using various phosphorylation site mutants and kinase and phosphatase inhibitors in pulse-chase experiments, we have found that although nascent CFTR can be phosphorylated at the ER, this is without effect on its ability to mature and avoid proteolysis. Furthermore, we found that microsomes from cells expressing CFTR processing mutants such as DeltaF508 do not generate Cl(-) active channels when fused with planar bilayers unless maturation is promoted, e.g. by growth of cells at reduced temperature or other means. We conclude that the ER-retained mutant nascent chains which are incapable of maturation may be phosphorylated but do not form active channels. Stimulation by PKA of the insertion of CFTR containing vesicles into the plasma membrane as part of the mechanism of stimulation of chloride secretion has been reported, as has an influence of CFTR on the balance between endocytosis and exocytosis but these findings have not been universally confirmed.
- Published
- 1999
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