In an experimental model of in vivo hyperthermia, we investigated the involvement of a number of signalling events in rat liver. We report that in vivo heat shock causes a powerful activation of c-Jun N-terminal kinase and p38 kinase but does not trigger poly(ADP-ribose) polymerase cleavage, a signature event of apoptosis. Among the upstream regulators of the kinases, we show that stress-activated protein kinase/extracellular signal-regulated kinase/nitrogen-activated protein kinase kinase 4 SEK1/MKK4 is not involved whereas MKK3 and/or MKK6 are activated. PAK activity displays a transient rise, whereas GCK does not change. PI3-kinase activity increases in anti-phosphotyrosine immunoprecipitates, suggesting a tyrosine kinase-dependent induction mechanism, and the co-immunoprecipitation of PI3-kinase with p60 Src kinase supports the involvement of this latter. GSK3, which may act downstream to PI3-kinase through AKT, undergoes hyperphosphorylation, thus playing a possible role in the protection from apoptosis and in the modulation of heat-shock transcription factor activity. (C) 2000 Academic Press.
|Titolo:||Cellular signalling after heat shock in the liver|
BENDINELLI, PAOLA (Secondo)
|Parole Chiave:||Heat shock; Rat liver; Signal transduction; Stress-activated protein kinases|
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
|Data di pubblicazione:||2000|
|Digital Object Identifier (DOI):||10.1006/cbir.1999.0493|
|Appare nelle tipologie:||01 - Articolo su periodico|