Cellular signalling after in vivo heat shock in the liver.
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.
Maroni
P
P
Istituto di Patologia Generale, Università degli Studi di Milano, Centro di Studio sulla Patologia Cellulare del CNR, Via Mangiagalli 31, Milan, 20133, Italy.
Bendinelli
P
P
Zuccorononno
C
C
Schiaffonati
L
L
Piccoletti
R
R
D000818:Animals; D018869:Heat-Shock Response / Q000502:physiology*; D008099:Liver / Q000201:enzymology*; D008297:Male; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology*; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases
D011065:Poly(ADP-ribose) Polymerases; D019869:Phosphatidylinositol 3-Kinases; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases