Proteins belonging to the Cbl family are multidomain scaffolds that participate in numerous processes, assembling signaling complexes and mediating attachment of ubiquitin to receptor and non-receptor tyrosine kinases. We characterized a novel role for Cbl and Cbl-b in ligand-dependent internalization of growth factor receptors. Upon stimulation with epidermal growth factor (EGF), Cbl proteins associate with EGF receptor, become phosphorylated, and bind to the three SH3 domains of CIN85, which brings endophilins to the complex with active receptors. Endophilins can induce internalization of the plasma membrane, contributing to formation of clathrin-coated pits. We identified a minimal binding domain for CIN85 in the carboxyl termini of Cbl/Cbl-b and observed constitutive association between CIN85, Cbl/Cbl-b and oncogenically stimulated receptor tyrosine kinases. In addition to functioning as a ubiquitin ligase, Cbl forms a complex with CIN85 and endophilin, which is required for efficient endocytosis and downregulation of membrane receptors. In EGF stimulated cells, we observed inducible modification of CIN85 and related CMS proteins by attachment of a single ubiquitin molecule. Monoubiquitination of CIN85 was mediated by the RING finger and dependent on the carboxyl terminal part of Cbl/Cbl-b, and demanded an intact carboxyl terminus of CIN85. Prolonged stimulation with EGF induced concomitant degradation of EGF receptors, Cbl, and monoubiquitinated forms of CIN85 in lysosomes. Cbl regulates cytoskeletal processes in a variety of cell systems. We identified SH3P2, a protein with SH3 domain and ankyrin repeats, as a Cbl partner and described its phosphorylation by Src and its distribution in fibroblasts and osteoclasts. SH3P2 formed inducible complexes with Cbl and actin in spread cells and colocalized with dynamic actin structures. Our data contribute to better understanding of the role of Cbl in downregulation of receptor tyrosine kinases as well as in controlling actin rearrangement.

En els darrers anys s´ha consolidat l´enfoc translacional en l´abordatge del càncer. Aquest es basa en la voluntat de comprendre la biologia tumoral i implementar clínicament aquest coneixement dissenyant nous fàrmacs capaços d´inhibir específicament molècules oncogèniques.En aquest context, s´han descobert els receptors tirosina-quinasa (RTK) com a proto-oncogens crucials en la diferenciació i proliferació cel·lular i com a molècules amb un gran paper en carcinogènesi. KIT i PDGFR són dos exemples paradigmàtics de RTK pels que s´han desenvolupat fàrmacs inhibidors, amb gran èxit terapèutic en aquells tumors, com el GIST, on aquestes proteïnes tenen un paper patogenètic crucial.L´enfoc translacional ha tingut un gran impacte en el camp dels tumors renals que representen un 3% dels tumors de l´economia i dels quals s´en reconeixen diferents subtipus. Els avenços en biologia molecular han permès definir la patogènia d´algunes entitats, sobretot del Carcinoma renal de cèl·lula clara (CRCC), un dels subtipus tumorals freqüents i més agressiu per l´alt nombre de pacients que desenvolupen malaltia metastàtica (30-50%) i pels quals s´estan buscant noves eines terapèutiques.Pel valor oncogènic i com a dianes terapèutiques del KIT i PGFR, aquest treball té com a objectiu estudiar l´expressió d´aquestes proteïnes per immunohistoquímica sobre teixit de tumors de cèl·lules renals. A més a més, en base a aquests resultats i la literatura es pretén discutir el seu valor com a dianes terapèutiques.En el nostre estudi es va demostrar expressió de KIT de forma específica en Carcinoma renal Cromòfob (ChRCC) i Oncocitoma (OR). També es va trobar sobreexpressió de KIT i PDGFRα en la diferenciació sarcomatoide de carcinomes renals (SRCC) sense que aquesta s´associès amb mutacions en els exons 9, 11, 13, 17 del KIT ni en els exons 11, 12, 17, 18 de PDGFRα; que són els més freqüent mutats en el GIST .Alhora vam observar expressió inespecífica en cèl·lules tumorals de PDGFRα i PDGFRβ en un baix nombre de casos i de forma dèbil en diferents subtipus de tumors renals. Per contra, vam evidenciar sobreexpressió de PDGFRβ vascular de forma característica en un alt percentatge de CRCC. En base als nostres resultats, proposem la utilitat de KIT com a marcador en el diagnòstic diferencial de diferents subtipus tumorals. Alhora, hem demostrat que l´expressió de KIT i PDGFRα en els SRCC no segueix el mateix model patogenètic que el GIST. La literatura sosté la necessitat de demostrar la implicació patogènica d´una proteïna en un tumor per plantejar l´efectivitat de la seva inhibició selectiva, essent l´expressió immunohistoquímica per si mateixa insuficient per sostindre aquest principi.Fins al moment, no es coneix si KIT i PDGFR tenen un paper oncogènic en el ChRCC, OR i en SRCC.Per tant, no hi ha suficients dades per proposar l´us d´inhibidors proteics contra aquestes proteïnes en ChRCC i SRCC disseminats.Per altra banda l´expressió vascular de PDGFRβ en CRCC si que té una base patogenètica ja que el seu lligand (PDGF) s´ha implicat directament en la seva biologia. Alhora aquesta expressió vascular és coherent amb els estudis que relacionen la isoforma beta del PDGFR amb la maduració dels pericits i en la promoció de l´angiogènesi.Per tant, els nostres resultats sostenen la relació del PDGFRβ en la patogènia del Carcinoma renal de cèl·lula clara i el valor terapèutic dels fàrmacs contra aquest receptor amb finalitat antiangiogènica.En conclusió, en el context de l´enfoc translacional del càncer i la necessitat d´implementació de nous fàrmacs inhibidors proteics pel tractament del carcinoma renal metastàtic, l´anàlisi d´expressió de RTK en tumors renals permet juntament amb la integració d´altres estudis, la discussió del valor diagnòstic i sobretot terapèutic d´aquestes dianes moleculars. / Renal Cell Neoplasms (RCN) represent 3% of cancer incidence and comprise different clinicopathologic entities. Malignant subtypes, specially the most frequent one Clear Cell Renal Cell Carcinoma (CRCC), remain the most lethal of urologic cancers due to the high rate of patients (30-50%) developing metastatic disease for whom new therapies are needed.Great advances in molecular biology have led to the identification of tyrosine-kinase receptors (TKR) as relevant proteins in tumorigenesis. Moreover the advent of selective inhibitors against them has raised interest on its expression in different tumors.PDGFR and KIT are two examples of TKR that have an oncogenic role in numerous neoplasms and can be inhibited pharmacologically. Because of its potential role as proto-oncogens and therapeutic targets; We aimed to study its immunohistochemical expression in RCN and to discuss its possible role as molecular targets.Our results highlight specific expression of KIT in Chromophobe renal cell carcinoma (ChRCC) and Renal Oncocytoma (RO). Overexpression of KIT and PDGFRα was found in sarcomatoid differentiation of renal tumours (SRCC) without mutations in KIT exons 9,11,13,17 nor PDGFR exons 11,12,17,18 which are the most commonly mutated in GIST.Moreover inespecific and low expression of PDGFRα and PDGFRβ was evidenced in tumoral cells in different RCN. In contrast, vascular expression of PDGFRβ was seen caracteristically in half of CRCC cases.According to our results, we propose KIT as a useful marker for differential diagnosis among RCN.Moreover we demonstrate that expression of KIT and PDGFR in SRCC doesn´t follow the same pathogenetic mecanism as GIST.Scientific community claims that immunohistochemical expression of a protein in a tumor is not enough to propose it as a therapeutic target and that demonstation of its pathogenetic role is needed. So as, there is still no evidence of participation of KIT-PDGFR in ChRCC, OR nor SRCC oncogenesis, there is not enough data to propose them as therapeutic targets.Conversely, in different studies PDGFRβ has been involved in CRCC pathogenesis and has been related to tumor angiogenesis by perycite recruitment. So that, vascular expression of PDGFRβ in CRCC favours its consideration as a therapeutic target in this tumor subtype.

Rapporten syftar till att avgöra om entreprenörernas stora användning av GNSSteknikinom vägbyggnation är berättigad med avseende på ställda toleranskrav.GNSS betyder ”Global Navigation Satellite Systems” och är ett samlingsnamn förde satellitsystem som idag används för att utföra precisionsmätningar.En litteraturstudie har gjorts för att få svar på frågorna om vilka toleranser somgäller för vägutsättning samt vilken noggrannhet de olika mätmetoderna har.Kontakt har tagits med ett antal vägentreprenörer från olika företag som är insattai vägutsättning. De har fått besvara ett antal frågor som reder ut vilkenmetod/utrustning de använder idag samt hur stor kunskapen är om GNSS iblandentreprenörerna. De har dessutom fått svara på vad de anser är för-, respektivenackdelar med användning av GNSS vid vägutsättning.En litteraturstudie av byggtoleranser resulterar i de värden som måste uppnås vidbygget. Dessa jämförs sedan med de noggrannheter som de olika mätmetodernahar enligt en litteraturstudie av dessa.Frågeformulär har skickats ut och sammanställs i rapporten vilket ger en godåterspegling av entreprenörernas åsikter och kunskaper om GNSS samt vad deanvänder sig av idag. Dessutom finns en sammanfattad punktlista med för ochnackdelar som angetts av mätansvariga hos de olika entreprenörerna.En slutsats som kan dras är att den beställare som använder sig av AMAAnläggning 07 vid upprättande av bygghandling också anger toleranskrav i bådeplan och höjd för alla vägens lager.Ska man jämföra mätnoggrannhet med de hjälptoleranser i höjd som beskrivits såär GNSS-tekniken otillräcklig för den noggrannheten som ställs. Dessahjälptoleranser speglar dock inte funktionskraven till fullo utan är bara ett slagshjälpmedel för att räkna ut rimliga utsättningstoleranser.Entreprenörer vittnar om att GNSS-teknik kan användas vid anläggning avsamtliga obundna lager undantaget bärlagerjustering för att uppfylla defunktionskrav som ställs på vägen. Detta verifieras med de efterkontroller somgörs på vägens färdiga lager.De entreprenörer som är vana vid större vägprojekt har även stor kunskap omGNSS-teknik och använder den flitigt.Det finns stora fördelar med användandet av GNSS-tekniken. Smidighet, en godöverblick för maskinföraren och tidsbesparing är några av demMen det finns även vissa nackdelar som dålig kompabilitet mellan olika märken påutrustning, onoggrannheten som inte tillåter att man helt slutar använda annan typav mätutrustning samt att platsansvariga tappar överblicken över bygget. / The report aims to determine whether contractors' high use of GNSS technologyin road construction is entitled in respect of subordinated tolerance requirements.GNSS means ”Global Navigation Satellite Systems” and is a collective name forthe satellite systems that today are used to perform precision measurements.A literature study has been done to get answers to questions about the tolerancesthat apply to road stake out and the accuracy of the different measurementmethods.Contact has been made with a number of road contractors from variouscompanies who are familiar with road stake out. They've got to answer a numberof questions that sorts out which method / equipment they use today and howmuch knowledge is on GNSS among contractors. They also answered questionsabout what they believe is for, and disadvantages with the use of GNSS in roadstake out.The literature review of construction tolerances results in the values that must beachieved during the construction. These results are then compared with theaccuracies of different measurement methods, according to the literature review ofthese.A questionnaire was sent out and responses are compiled in the report, they giveus a good reflection of contractors' opinions and knowledge of GNSS and whatthey use today. A bulleted list has been made of pros and cons identified bypersons responsible of measuring among the various contractors.A conclusion to be drawn is that the client that uses the AMA Anläggning 07 inthe preparation of construction document also specifies tolerances of all layers ofthe road, both horizontally and vertically.Shall one compare accuracy of GNSS technology with the help tolerances inheight described in the report; the method is inadequate for the accuracyrequirements. These tolerances are not fully comparable to the performancerequirements; it is only a tool to figure out a reasonable stake out tolerances.Contractors testify that GNSS technology can be used in the construction of allunbound layers except for base course adjustments to meet the functionaldemands on the road.The contractors who are accustomed to major road projects have also greatknowledge of GNSS technology and use it diligently. There are great benefits withthe use of GNSS technology. Agility, a good overview for the machine operatorand time saving are some of them. But there are also some disadvantages such aspoor compatibility between different brands, inaccuracy that does not allow tocompletely stopping using other types of measuring equipment and locationmanagers that loses the overview.

Fledermaus is software where different kind of analysis with spatial data can be done. The main area where to use Fledermaus is related to hydrographical surveys. This study is aimed to test and analyse the way Swedish Maritime Administration (Sjöfartsverket) uses Fledermaus. Through step by step explaining how to do when measuring sea bed conditions from a vessel, this text is possible to use as a manual for the applications that are mentioned in this report. Another thing that is treated is the squat effect that belongs to vessel dynamic motions. Test of visualization that concerning squat in Fledermaus is done, but with a negative result when squat in a perspective to show motions in height that can be up to about a metre is very hard in a terrain model of thousands of metres. By further tests by arranging the input data, several interesting diagrams have been created through Microsoft Excel where graphs show that the depths are affecting the squat effect. This is showed in same diagram but with two different scales to show the relationship between how a point at the vessel moves in height compared to the depth under the vessel when the vessel is navigating in the sea. / Fledermaus är en programvara där olika analyser med rumsliga data kan genomföras. Största användningsområdet är att använda Fledermaus till mätningar som är relaterade till sjömätning. Den här studien är inriktad till att testa och analysera applikationer som Sjöfartsverket använder sig av i Fledermaus. Genom att steg för steg förklara hur Fledermaus ska användas när bottenförhållanden ska mätas sett från ett fartyg, så blir texten även möjlig att använda som en manual till de applikationer i Fledermaus som är nämnda i denna rapport. Det andra som behandlas är squateffekten som tillhör ett fartygs dynamiska rörelser. Test av visualisering som behandlar squat i Fledermaus är genomförd, dock med negativt resultat då squat i ett perspektiv med att visa rörelser i höjd som kan uppgå till runt en meter är väldigt svårt i en terrängmodell som sträcker sig tusentals meter. Dock genom vidare tester genom behandling av indata, har flertalet intressanta diagram skapats genom Microsoft Excel där kurvor visar att djupet inverkar på squateffekten. Detta visas genom att i samma diagram fast med två olika skalor visa förhållandet mellan hur en punkt på båten rör sig i höjd jämfört med att djupet under fartyget ändras då fartyget gör fart genom vattnet.

The Caenorhabditis elegans Eph RTK, VAB-1, has known roles in neuronal and epidermal morphogenesis as well as oocyte maturation through interaction with its ephrin ligands. In humans, Eph receptors are involved in nervous and vascular system development and have been implicated in cancer formation and progression. DAF-18, a C. elegans ortholog of the human tumour suppressor gene, PTEN, has been identified as an interacting partner with the Eph RTK, VAB-1. Mutations in human PTEN have been associated with numerous cancers and in the worm, DAF-18 is a well studied member of the DAF-2/Insulin receptor-like signaling pathway which has roles in dauer formation, thermotolerance and adult longevity. Our lab has previously shown that VAB-1/EphR binds DAF-18. To further investigate the significance of this interaction as well as offer additional function to the proteins involved, I have shown that VAB-1/EphR is a negative regulator of DAF-18/PTEN at the protein level. Western blotting reveals that endogenous expression of DAF-18/PTEN is low in wild-type animals and expression is increased in a vab-1/ephR mutant. Additionally, VAB-1/EphR and DAF-18/PTEN are expressed in head neurons, oocytes and the germline precursor cells, Z2/Z3. vab-1/ephR mutants show increases longevity and sensitivity to dauer conditions which is consistent with increased DAF-18/PTEN activity. Lastly, daf-18(ok480) is able to suppress the oocyte maturation phenotype and increased MAPK expression displayed by vab-1(dx31) animals, providing genetic evidence of an interaction. By identifying the tissues where these proteins are co-expressed and substantiating the interaction with multiple analyses, novel roles may be proposed for each: VAB-1/EphR in DAF-2/Insulin signaling and DAF-18/PTEN in oocyte maturation downstream of VAB-1/EphR signaling. This work provides further understanding of how an organism coordinates complex developmental processes and reiterates the notion that cellular signaling is a complex network of interacting players. As many signaling pathways are evolutionarily conserved, my research in C. elegans may provide a mechanism on how Eph RTKs and PTEN are regulated in more complex organisms, including humans. / Thesis (Master, Biology) -- Queen's University, 2009-02-27 17:09:10.582

In Drosophila melanogaster the visceral mesoderm (VM) develops during embryogenesis in a process where myoblasts become specified to generate two distinct cell types, the founder cells (FCs) and the fusion competent myoblasts (FCMs) that consequently fuses. The cell specification is dependent on cell signaling mediated by the receptor tyrosine kinase (RTK) Anaplastic lymphoma kinase (Alk) and its ligand Jelly belly (Jeb), how this further sets up different identity programs that drive myoblasts to differentiate into FCs and FCMs is still not well understood. We have analysed whether the Midkine (MDK)/Pleiotrophin (PTN) homologues in Drosophila, Miple1 and Miple2 activate the Alk RTK in vivo. Earlier results from cell culture experiments suggested that vertebrate MDK/PTN is capable of activating ALK, findings that have become controversial with other studies showing contradictory results. We wanted to use Drosophila that have conserved homologues of both MDK/PTN and ALK, to address the question in vivo. We analysed the contribution of Miple in Alk dependent developmental processes such as visceral mesoderm (VM) specification during embryogenesis and in body size regulation of adult flies. Specification of VM as well as body size are not effected by loss of Miple proteins, and over expression of Miple proteins do not effect VM specification or body size. All together we conclude that there is no evidence that Miple1 or Miple2 can activate Alk in vivo. We found that loss of Miple protein effect the median lifespan of the fly which is reduced, interestingly the over expression of Miple proteins can promote an increased median life span in Drosophila. We have also analysed how Alk RTK signaling regulates the Gli-like transcription factor Lame duck (Lmd) in vivo on a post-translational level. It has already been reported that Lmd plays an essential role in specification of FCMs in the somatic mesoderm during embryogenesis. We detect Lmd protein exclusively in FCMs of VM in control embryos, but in Alk mutants Lmd protein is present in all cells of VM and opposite to this when Alk is activated in all cells in VM by over expression of Jeb this results in total loss of Lmd protein. This suggests that Alk signaling is regulating Lmd, and we additionally show that Lmd persist in FCMs in mutants where VM is specified but where myoblast fusion do not occur, supporting that Alk activity in FCs is regulating the downregulation of Lmd in FCMs upon fusion. Finally we have characterised the Rap1GEF C3G in vivo in Drosophila. In cell culture systems, the GTPase Rap1 has been identified to mediate Alk signaling and that this is regulated by the GEF C3G and interestingly the Drosophila C3G is expressed in the FCs of VM. We generated deletion mutants of C3G which exhibit semi-lethality and reduced life span, but no defects in visceral mesoderm development during embryogenesis. Instead we detected distinct phenotypes in somatic muscles of 3rd instar mutant larvae, with detachment and mistargeting of muscles, which effect localisation of integrins. We suggest that Drosophila C3G regulates Rap1 via inside out signaling of integrins which in turn effects cell adhesion in vivo in Drosophila larval muscles.

Many high-accuracy regional GPS continuously operating reference (CORS) networks have been established globally. These networks are used to facilitate better positioning services, such as high accuracy real-time positioning. GPSnet is the first state-wide CORS network in Australia. In order to maximize the benefits of the expensive CORS geospatial infrastructure, the state of Victoria in collaboration with three universities (RMIT University, the University of NSW and the University of Melbourne) embarked on research into regional atmospheric error modelling for Network-based RTK (NRTK) via an Australian Research Council project in early 2005. The core of the NRTK technique is the modelling of the spatially-correlated errors. The accuracy of the regional error model is a determining factor for the performance of NRTK positioning. In this research, a number of error models are examined and comprehensively analysed. Among them, the following three models are tested: 1) the Linear Interpolation Method (LIM); 2) the Distance-Based interpolation method (DIM); and 3) the Low-order surface model (LSM). The accuracy of the three models is evaluated using three different observation sessions and a variety of network configurations of GPSnet. Results show that the LIM and DIM can be used to significantly reduce the double-differenced (DD) residuals (up to 60% improvement), and the LIM is slightly better than the DIM (most at mm level). However the DD residuals with the LSM corrections are, in some cases, not only much worse than that of the LIM and DIM but also even must greater/worse than the DD residuals without any corrections applied at all. This indicates that there are no advantages by using the LSM for the error modelling for NRTK in GPSnet, even though it is the most commonly used method by researchers. The performance difference of the LIM for different GPSnet configurations is also tested. Results show that in most cases, the performance difference mainly caused by the number of reference stations used is not significant. This implies that more redundant reference stations may not contribute much to the accuracy improvement of the LIM. However, it may mitigate the station specific errors (if any). The magnitude of the temporal variations of both the tropospheric and ionospheric effects in GPSnet observations is also investigated. Test results suggest that the frequency of generating and transmitting the tropospheric corrections should not be significantly different from that for the ionospehric corrections. Thus 1Hz frequency (i.e. once every second) is recommended for the generation and transmission for both types of the atmospheric corrections for NRTK in GPSnet. The algorithms of the NRTK software package used are examined and extensive analyses are conducted. The performance and limitation of the NRTK system in terms of network ambiguity resolution are assessed. The methodology for generating virtual reference station (VRS) observations in the system is presented. The validation of the algorithms for the generated VRS observations is undertaken. It is expected that this research is significant for both the selection of regional error models and the implementation of the NRTK technique in GPSnet or in the Victorian region.

Från den 1 april 2006 gavs möjligheten att använda GLONASS-systemet vid NRTK-mätningar som dessförinnan enbart använde sig av GPS-systemet. Allt fler inbyggda positioneringstjänster i vår nya teknik går nu mot att börja använda sig av både GPS och GLONASS-systemen. Tillgången till både amerikanska och ryska satelliter borde göra att vi får bättre, mer exakta och stabila mätningar vid dåliga förhållanden. Men är verkligen följden av att använda fler satelliter lösningen, eller räcker det i vissa tillfällen med enbart GPS-satelliter. Är den mer utbreda användningen av GLONASS-satelliter bara marknadsföring från företagen för att få sälja mer, dyrare och nyare produkter och därmed lura konsumenten att den är i behov av uppgraderade produkter som har GLONASS-stöd. Syftet var att undersöka om GPS och GLONASS förbättrar mätningarna och tillgängligheten i öppna respektive störda miljöer eller är det bara onödigt för konsumenten att sträva efter att positioneringsverktyget i ny teknik ska stödja båda satellitsystemen. En annan fråga är om det finns viss ny teknik som är tillämpade för olika områden där behovet är antingen större av GPS och GLONASS eller de områden där enbart GPS räcker till och ger minst lika goda mätningar och positionering. I detta examensarbete gjordes NRTK mätningar mot SWEPOS på ett antal kända punkter vid Karlstads Universitet där punkterna hade olika förutsättningar så som öppna och störda miljöer. Mätningarna gjordes med enbart GPS- respektive med GPS och GLONASS-satelliter påslagna. De bestämda koordinaterna i plan för de kända punkterna jämfördes med koordinaterna från mätningarna med enbart GPS respektive med GPS och GLONASS. De extra GLONASS-satelliterna är bra att använda sig av när man ska mäta i störda miljöer, de hjälper till att få en bättre noggrannhet. När man dock är i icke störda miljöer med fri sikt mot satelliterna räcker enbart GPS-satelliterna långt. Med den nya tekniken som kommer så finns ofta GLONASS-systemet inbyggt och är i de flesta fall är ingen ytterligare kostnad som konsumenten behöver ta utan är endast ett bra komplement oavsett användningsområde.

Within the immune system, Y-shaped proteins known as antibodies play crucial roles in detecting and blocking the harmful effects of foreign pathogens. Antibodies are naturally synthesized in our bodies by plasma B-cells, but they can also be synthesized and manufactured in labs through methods of recombinant antibody technology. Today, the field of antibody research and development is a competitive area of study due to the great promise it carries. In this study, 4 clones were developed as phage linked and soluble scFv proteins in order to be tested for their specificity against an RTK antigen, T1. T1 was of interest due to its hypothesized involvement in a breast cancer causing pathway. Subsequent selection assays in the form of ELISA and Western Blot were performed in order to identify a promising antibody candidate both robust in expression and specific in binding. The ELISA results pointed to Clone A1 as having the greatest potency and specificity for the T1 target antigen when it was presented as a phage linked and soluble scFv protein. Evaluation of the expression profiles for the 4 soluble and phage linked clones also pointed to clone A1 as being the most robust and potent. In conclusion, clone A1 exhibited the greatest ability in expression and detection of the T1 antigen and was thereby determined to be the most promising candidate in further development and optimization procedures. A1’s results in the preliminary tests also suggests strong performance in its translation into a successful therapeutic drug.

he main subject of this thesis is accuracy testing of three GNSS RTK receivers – Trimble R4, Leica 1200, Topcon GRS-1. It is an outdoor research using different correction types provided by CZEPOS and Trimble.