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FcεRI and Kit signal to actin cytoskeleton via different pathways
Šimíček, Michal ; Drbal, Karel (referee) ; Dráber, Petr (advisor)
Mast cells are key effector cells of the immune system whose exact physiological functions have been the subject of much debate. They have been mentioned mostly as the drivers of allergic and inflammatory reactions via allergens triggering their high affinity receptors for IgE (FcεRI). However, recent findings implicate their important role also in other innate immune functions like host protection from bacterial and viral infections. Agent recognized by surface receptor initialize various intracellular signaling pathways leading to cell response. Thus, better understanding of signal transduction in mast cells is important in development of new therapeutic approaches. Early phases of mast cell activation mediated by FcεRI and/or Kit, a receptor for stem cell factor (SCF), involve phosphorylation of the transmembrane adaptor protein Non-T cell activation linker (NTAL) and mast cell spreading. Morphological studies of mast cells derived from bone marrow of mice deficient in NTAL (NTAL knock out, NTAL -/-) revealed markedly reduced spreading on fibronectin after stimulation with antigen (Ag) alone or in combination with SCF, when compared to wild type (WT) cells. Subsequent quantification of cell area and analysis of other mophological parameters confirmed these observations. Mast cell activation was...
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Comparative genomic prediction of novel transmembrane adaptor proteins and their expression analysis.
Pitule, Pavel ; Novotný, Marian (referee) ; Drbal, Karel (advisor)
Transmembrane adaptor proteins play an important role in signal transduction cascades emanating from immune cell receptors leading to cellular effector mechanisms. Despite the lack of enzymatic function, their sequence contains interaction motifs which organize other proteins in time and space and initiates building of the signaling complexes. Functionally the most important and for the longest time known TRAPs are the ones associated with immune receptors. Their deficiency has severe impacts on the signal transduction and knock-out mice show dramatic phenotypes. The deficiency of Lat - the first discovered TRAP, which is not constitutively associated with immune receptors - has comparable effects on signaling in lymphocytes. The difference between the first group of TRAPs and Lat is not only the type of association with receptors, but also the lack of tyrosine - based activation motifs (ITAMs) in Lat, but Lat contains several other binding motifs also based on the phosphorylation of tyrosine. The group of TRAPs similar to Lat up today contains eight members, but all of them, except of Lat, has only very mild or undetectable phenotype in the knock-out mice. In this work I searched the protein databases for proteins with the characteristics of TRAP using the bioinformatic tools. Based on our...
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Analysis of candidate transmembrane adaptor proteins
Šulcová, Jitka ; Černý, Jan (referee) ; Drbal, Karel (advisor)
Transmembrane adaptor proteins (TRAPs) function as a scaffolding anchor for numerous signaling molecules and facilitate formation of large signaling complexes near the plasma membrane. They regulate spatio-temporal organization of signaling events in order to transduce fast and effective signal from surface receptors into the cell nucleus. The importance of described TRAPs in the development and proper functioning of immune cells in relation to their localization within lipid rafts is still under debate. The simple reason is the lack of a profound phenotype in knock-out mice. The described phenotypes observed in animals deficient in ITAM-containing adaptors of immunoreceptors as well as lipid raft adaptor Lat all lead to the block in the T-cell development and impaired TCR signaling. The subject of my diploma thesis is to perform bioinformatic search and filter candidate TRAP genes according to predicted and published data. Selected TRAP candidates were subjected to functional characterization. I checked for their localization to the plasma membrane and correlate their ectopic overexpression with the expression of CD69 surface Tcell activation marker. From 14 candidate TRAPs, only a single Pdzk1ip1 protein is probably localized to the plasma membrane but its expression does not influence CD69...
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Paleomagnetický výzkum sedimentárních výplní vybraných jeskyní v České republice : závěrečná zpráva k výjimce MŽP ČR
Bosák, Pavel ; Hercman, H. ; Kadlec, Jaroslav ; Pruner, Petr ; Schnabl, Petr ; Hlaváč, Jaroslav ; Drahotová, Jana ; Pavková, Jaroslava ; Petráček, Jiří ; Rajlichová, Jana ; Drbal, K. ; Komaško, A. ; Milka, D.
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