134 research outputs found
Therapie des Hepatozellulären Karzinoms durch RNAi-vermittelte Suppression der Plk1-Expression
No full textRegulation of the interaction between protein kinase C-related protein kinase 2(PRK2) and its upstream kinase, 3-phosphoinositide-dependent protein kinase 1 (PDK1)
No full textRole of the Z-/turn motif and of the N-Terminus of PRK2 in the regulation of the interaction between protein kinase C-related protein kinase 2 (PRK2) and 3-phosphoinositide dependent protein kinase 1 (PDK1)
No full textRegulation of the interaction between protein kinase C-related protein kinase 2(PRK2) and its upstream kinase, 3-phosphoinositide-dependent protein kinase 1 (PDK1)
No full textACE2, the Receptor that Enables Infection by SARS‐CoV‐2: Biochemistry, Structure, Allostery and Evaluation of the Potential Development of ACE2 Modulators
No full textAngiotensin Converting Enzyme 2 (ACE2) is the human receptor that interacts with the Spike protein of coronaviruses, including the one that produced the 2020 coronavirus pandemic (COVID-19). Thus, ACE2 is a potential target for drugs that disrupt the interaction of human cells with SARS-CoV-2 to abolish infection. There is also interest on drugs that inhibit or activate ACE2, i.e. for cardiovascular disorders or colitis. Compounds binding at alternative sites could allosterically affect the interaction with Spike protein. We here review biochemical, chemical biology and structural information on ACE2, including the recent cryoEM structures of full length ACE2. We conclude that ACE2 is very dynamic and that allosteric drugs may be developed to target ACE2. At the time of the 2020 pandemic, we suggest that available ACE2 inhibitors or activators in advanced development should be tested for their ability to allosterically displace the interaction between ACE2 and the Spike protein.Fil: Gross, Lissy Zoe Florens. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Sacerdoti, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Piiper, Albrecht. Goethe Universitat Frankfurt; AlemaniaFil: Zeuzem, Stefan. Goethe Universitat Frankfurt; AlemaniaFil: Leroux, Alejandro Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Biondi, Ricardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentin
Regulation of protein kinase C-related Protein Kinase 2 (PRK2) by an intermolecular PRK2-PRK2 interaction mediated by its N-terminal domain
No full textProtein kinase C-related protein kinases (PRKs) are effectors of the Rho family of small GTPases and play a role in the development of diseases such as prostate cancer and hepatitis C. Here we examined the mechanism underlying the regulation of PRK2 by its N-terminal region. We show that the N-terminal region of PRK2 prevents the interaction with its upstream kinase, the 3-phosphoinositide-dependent kinase 1 (PDK1), which phosphorylates the activation loop of PRK2. We confirm that the N-terminal region directly inhibits the kinase activity of PRK2. However, in contrast to previous models, our data indicate that this inhibition is mediated in trans through an intermolecular PRK2-PRK2 interaction. Our results also suggest that amino acids 487-501, located in the linker region between the N-terminal domains and the catalytic domain, contribute to the PRK2-PRK2 dimer formation. This dimerization is further supported by other N-terminal domains. Additionally, we provide evidence that the region C-terminal to the catalytic domain intramolecularly activates PRK2. Finally, we discovered that the catalytic domain mediates a cross-talk between the inhibitory N-terminal region and the activating C-terminal region. The results presented here describe a novel mechanism of regulation among AGC kinases and offer new insights into potential approaches to pharmacologically regulate PRK2.Fil: Bauer, Angelika F.. Goethe Universitat Frankfurt; AlemaniaFil: Sonzogni, Silvina Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria; Argentina. Goethe Universitat Frankfurt; AlemaniaFil: Meyer, Lucas. Goethe Universitat Frankfurt; AlemaniaFil: Zeuzem, Stefan. Goethe Universitat Frankfurt; AlemaniaFil: Piiper, Albrecht. Goethe Universitat Frankfurt; AlemaniaFil: Biondi, Ricardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria; Argentina. Goethe Universitat Frankfurt; AlemaniaFil: Neimanis, Sonja. Goethe Universitat Frankfurt; Alemani
Choosing a Co-Operation Partner for Enterprise Easy Wireless Services OÜ
No full textAntud lõputöö eesmärgiks on välja selgitada kolm võimalikku koostööpartnerit ettevõttele Easy Wireless Services OÜ väikepakkide saatmiseks- ja tagastamiseks Eesti, Läti ja Leedu piires arvestades piirkonda, tarneaega ning maksumust. Eesmärgi saavutamiseks kasutas autor juhtumiuuringut, mille käigus tutvus teema kohas kirjanduse, ettevõtte Easy Wireless Services OÜ vajadustega ning selgitas välja ettevõtte äristrateegia põhjal kolm kõige sobivamat kullerettevõtet. Kullerettevõtete algse valimi saavutas autor Inforegistri keskkonna jaotuse „Muu posti- ja kulleriteenistus“ alusel. Autor seadis tingimuseks, et ettevõte peab omama kodulehekülge internetis. Saadud valimist selgitas autor välja 10 kullerettevõtet, arvestades ettevõtte Easy Wireless soove: ettevõte peab pakkuma uksest ukseni teenust vähemalt Eestis, Lätis ja Leedus ning võimalusel ka üldiselt kogu Euroopas. Kuna Inforegistris tehtud kitsenduse tõttu jäid kõrvale mitmed kullerettevõtted, lisas autor kuus ettevõtet valimisse juurde. Nii moodustus edasiseks analüüsiks valim, mis koosnes 15 ettevõttest. Valimis sisalduvate kullerettevõtete hindamiseks ning hilisemaks reastamiseks moodustas autor ettevõtte Easy Wireless Services OÜ äristrateegia põhjal seitse kõige olulisemat kriteeriumit, mis tähtsuse järjekorras on järgnevad: 1. teenindust hõlmavate riikide arv; 2. sihtpunktide arv antud riikides; 3. kullerteenuse olemasolu; 4. teenuse hind; 5. tarnekiirus; 6. teeninduspunktide olemasolu; 7. teeninduspunktide lahtiolekuaeg. Antud kriteeriumeid hindas autor kolme punkti skaalal ning kullerettevõtte hindepunktide arvutamiseks kasutas kriteeriumi kaalukuse ning saadud punktide korrutise summat. Võimalikke koostööpartnerite hindamise tulemusel jäid kolmandale ja neljandale kohale võrdsete punktidega kaks kullerettevõtet, mille seast ettevõtte Easy Wireles Services OÜ jaoks selgitas autor välja parema valiku seitsme olulise kriteeriumi kõige tähtsama teguri põhjal – sihtriikide arv ning nendes asuv võrgustik. Lõputöö tulemusel pakub autor ettevõttele Easy Wireless Services OÜ ning üldiselt väike pakke saatvatele ettevõtetele Euroopa siseselt kullerettevõtteid DPD Eesti AS, Cargobus OÜ ja HRX AS.Easy Wireless Services OÜ is a marketing and service company which provides wireless waiter calling systems for its customers. Customers are restaurants, cafes, pubs, clubs, hotels, motels, or other places where is a lot of work for waters. Easy Wireless Services OÜ has a problem how it would be useful to send systems to customers and how to manage reverse flows of material from customers back into company. Reverse flow is caused by returning of systems after testing periods or sending systems to maintenance. To achieve the goal, the author set a target to find information for these aspects: 1. Identify the co-opertion needs in the company; 2. How to indentify courier companies which are operating mainly in Estonia, Latvia, Lithuania and also in the whole Europe: 3. What are the main value indicators to find out courier companies which respond to Easy Wireless Services OÜ needs; 4. Courier companies which respond to Easy Wireless Services OÜ needs – provide door-to-door service at least in Estonia, Latvia, Lithuania and also in Europe: 5. To find three courier companies which provide service in the optimal way. Firstly, to reach the purpose the author worked through literature. Secondly, the author collected information by interviewing the Chief Executive Officer of the company Easy Wireless Services OÜ. Thirdly, the author found a method to determine courier companies which are registered in Estonia. Courier companies are selected out from the site Inforegister where it is possible to choose a criteria „Other postal and courier activities“. Due to the fact Inforegister does not contain all courier companies, the author added some potential co-operation partners to the couriers list. The main list consist of 15 courier companies. After that, the author named indicators and importances which are: 1. Countries and regions in the country where courier company acts – importance 4; 2. Service price – importance 3; 3. Delivery time – importance 3; 4. How many days can a courier company serve customers its door-to-door service? – importance 2; 5. How many offices does courier company have? – importance 2; 6. When are the offices opened? – importance 1. All the indicators were valued in three-point system. After evaluating courier companies the author found three companies which offer door-to-door service in a optimal way in Estonia, Latvia, Lithuania and also in whole Europe. These three companies are: 1. DPD Eesti AS; 2. Cargobus OÜ; 3. HRX AS. The author recommends using these three courier companies. But at the same time, it is useful to estimate also other companies because offered services change in time and also company Easy Wireless Services OÜ needs may change
Inositol 1,4,5-trisphosphate and 5′-GTP induce calcium release from different intracellular pools
No full textAbstractIt has been shown recently by several groups that 5′-GTP can release calcium from intracellular compartments independently from inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) by a mechanism which seems to be different from that used by Ins(1,4,5)P3. We report here for the first time that the 5′-GTP-sensitive and the Ins(1,4,5)P3-sensitive calcium pools reside in different intracellular compartments
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