The ERK (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 S6 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 ERK, 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.

• Klíčová slova
• 4-hydroxytamoxifen, 4HT, ALLM, ALLN, Calpain, Cell–cell junctions, EMT, ER, MAPK/ERK, MDCK, Madin–Darby Canine Kidney, Migration, N-Acetyl-l-leucine-l-leucine-l-norleucinal, N-Acetyl-l-leucyl-l-leucyl-l-methional, Polarity, RSK, epithelial–mesenchymal transition, ligand binding domain of estrogen receptor,
• MeSH
• buněčné linie MeSH
• epitelové buňky cytologie   metabolismus   MeSH
• extracelulárním signálem regulované MAP kinasy metabolismus   MeSH
• kadheriny metabolismus   MeSH
• kalpain metabolismus   MeSH
• kinasy ribozomálního proteinu S6, 90-kDa metabolismus   MeSH
• lidé MeSH
• MAP kinasový signální systém MeSH
• mezibuněčné spoje metabolismus   MeSH
• pohyb buněk MeSH
• polarita buněk MeSH
• psi MeSH
• signální transdukce * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• psi MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• extracelulárním signálem regulované MAP kinasy MeSH
• kadheriny MeSH
• kalpain MeSH
• kinasy ribozomálního proteinu S6, 90-kDa MeSH