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Functional analysis of the ERK signaling pathway in epithelial cells
Galvánková, Kristína ; Vomastek, Tomáš (advisor) ; Rösel, Daniel (referee)
The MAPK/ERK pathway, which is evolutionarily conserved in eukaryotes is one of the most intensively studied signaling pathways and consists of a three-tier cascade of Raf- MEK-ERK protein kinases. A variety of extracellular signals are transduced from receptors to hundreds of substrates by a series of sequential phosphorylations leading from Raf to MEK to ERK. The ERK pathway regulates a plethora of cell- and extracellular signal- specific responses such as gene expression, proliferation, differentiation, migration, and apoptosis. The proper execution of these physiological processes requires a precise temporal and spatial regulation of the pathway and disruption of the regulatory mechanisms leads to pathological consequence such as tumor transformation. Specificity and regulation of signal transduction are provided in part by the presence of isoforms at each level of the ERK signaling pathway. The functional differences between the effector protein kinases ERK1 and ERK2 have been controversial for a long time, but it is still unclear how important they are in achieving an appropriate cellular response. In this work, we focused on the functional characterization of ERK1 and ERK2 isoforms in MDCK epithelial cells. Specifically, we examined the effects of ERK2 inactivation on cell morphology and...
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The role of ERK1 and ERK2 protein kinases in the MAPK/ERK signaling
Galvánková, Kristína ; Vomastek, Tomáš (advisor) ; Dráber, Peter (referee)
The MAPK/ERK cascade is highly conserved signalling pathway regulating cellular processes which are necessary for cell life, such as proliferation, differentiation, apoptosis or cell migration. All these cellular responses are the result of the processing of extracellular signals through three-tier ERK cascade consisting of protein kinases Raf, MEK and ERK. The signal is transmitted by sequential phosphorylation where RAF phosphorylates MEK and MEK phosphorylates and activates ERK. Protein kinase ERK then phosphorylates and regulates a wide range of substrates at different locations in the cell. This affects the cellular response to the extracellular signal. Regulation of this pathway on every level is very important and is modulated by interaction partners and adaptor proteins. Deregulation of the pathway as well as mutations of individual protein kinases can lead to severe pathological consequences. At the level of ERK, there are two isoforms, ERK1 and ERK2, which are more than 80 % identical at the amino acid level. Their high sequence similarity has triggered the interest of many authors for more detailed examination of both isoforms in respect of their evolutionary conservation and whether they are functionally redundant or whether they have specific functions. The aim of this work is to...
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