CELLULAR SIGNALLING AFTER IN VIVO HEAT SHOCK IN THE LIVER

✍ Scribed by Paola Maroni; Paola Bendinelli; Cinzia Zuccorononno; Luisa Schiaffonati; Roberta Piccoletti

• Publisher: Elsevier Science
• Year: 2000
• Tongue: English
• Weight: 485 KB
• Volume: 24
• Category: Article
• ISSN: 1065-6995
• DOI: 10.1006/cbir.1999.0493

✦ Synopsis

Abstract

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.