0422123 - MBÚ 2014 RIV US eng J - Článek v odborném periodiku
Čáslavský, Josef - Klímová, Zuzana - Vomastek, Tomáš
ERK and RSK regulate distinct steps of a cellular program that induces transition from multicellular epithelium to single cell phenotype.
Cellular Signalling. Roč. 25, č. 12 (2013), s. 2743-2751. ISSN 0898-6568. E-ISSN 1873-3913
Grant CEP: GA ČR GA204/09/0614; GA ČR GA13-06405S
Institucionální podpora: RVO:61388971
Klíčová slova: MAPK/ERK * RSK * Polarity
Kód oboru RIV: EE - Mikrobiologie, virologie
Impakt faktor: 4.471, rok: 2013 ; AIS: 1.493, rok: 2013
DOI: https://doi.org/10.1016/j.cellsig.2013.08.024

The ERR (extracellular signal-regulated kinases) cascade has an evolutionarily conserved three tier architecture consisting of protein kinases Raf, MEK (MAPK/ERK kinase) and ERK Following activation, ERK phosphorylates various cellular elements leading to diverse cellular responses. Downstream of ERK the family of p90 ribosomal 56 kinases (RSKs) has been proven to be an important conveyor of ERK signaling, however, little is known if ERK and RSK coordinate their functions to generate a specific biological response. Here we show that in epithelial cells conditional activation of the ERK pathway causes phenotypic conversion of epithelial cells to autonomously migrating cells, This process involves two sequential steps characterized by loss of apical-basal polarity followed by cell scattering. The activation of ERR, but not RSK, is sufficient for the execution of the first step and it requires calpain mediated remodeling of actin cytoskeleton. Conversely, RSK regulates the successive stage characterized by cell-cell contact weakening and increased cellular migration. Thus, ERK and RSK regulate different cellular subprograms and coordinated execution of these subprograms in time generates a relevant biological response. Our data also suggest that the mechanism by which the ERK pathway controls a cellular response may be distributed between ERK and RSK, rather than being elicited by a single effector kinase
Trvalý link: http://hdl.handle.net/11104/0228341