The activation of kinases of the mitogen-activated protein kinase superfamily initiated by lipopolysaccharide (LPS) plays an important role in transducing inflammatory signals. The pathway leading to the induction of stress-activated protein kinases in macrophages stimulated with LPS was investigated. The activation of Jun N-terminal kinases (JNK) by LPS is herbimycin sensitive. Using specific inhibitors, it was shown that the pathway involves the activation of phosphoinositide 3-kinase (PI 3-K). However, in contrast to previous reports, the small GTPases Cdc42 and Rac are not required downstream of PI 3-K for JNK activation. Instead, the phosphoinositides produced by PI 3-K stimulate protein kinase C (PKC) zeta activation through PDK1. In turn, activation of this atypical PKC leads to the stimulation of phosphatidylcholine phospholipase C (PC-PLC) and acidic sphingomyelinase (ASMase). It is therefore proposed that PKCzeta regulates the PC-PLC/ASMase pathway, and it is hypothesized that the resultant ceramide accumulation mediates the activation of the SEK/JNK module by LPS.

Procyk, K., Rippo, M., Testi, R., Hofmann, F., Parker, P., Baccarini, M. (2000). Lipopolysaccharide induces jun N-terminal kinase activation in macrophages by a novel Cdc42/Rac-independent pathway involving sequential activation of protein kinase C zeta and phosphatidylcholine-dependent phospholipase C. BLOOD, 96(7), 2592-2598.

Lipopolysaccharide induces jun N-terminal kinase activation in macrophages by a novel Cdc42/Rac-independent pathway involving sequential activation of protein kinase C zeta and phosphatidylcholine-dependent phospholipase C

TESTI, ROBERTO;
2000-10-01

Abstract

The activation of kinases of the mitogen-activated protein kinase superfamily initiated by lipopolysaccharide (LPS) plays an important role in transducing inflammatory signals. The pathway leading to the induction of stress-activated protein kinases in macrophages stimulated with LPS was investigated. The activation of Jun N-terminal kinases (JNK) by LPS is herbimycin sensitive. Using specific inhibitors, it was shown that the pathway involves the activation of phosphoinositide 3-kinase (PI 3-K). However, in contrast to previous reports, the small GTPases Cdc42 and Rac are not required downstream of PI 3-K for JNK activation. Instead, the phosphoinositides produced by PI 3-K stimulate protein kinase C (PKC) zeta activation through PDK1. In turn, activation of this atypical PKC leads to the stimulation of phosphatidylcholine phospholipase C (PC-PLC) and acidic sphingomyelinase (ASMase). It is therefore proposed that PKCzeta regulates the PC-PLC/ASMase pathway, and it is hypothesized that the resultant ceramide accumulation mediates the activation of the SEK/JNK module by LPS.
1-ott-2000
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/04 - PATOLOGIA GENERALE
English
Androstadienes; Macrophages; Enzyme Activation; Enzyme Inhibitors; Sphingomyelin Phosphodiesterase; Benzoquinones; Lactams, Macrocyclic; Phosphatidylinositol 3-Kinases; Quinones; MAP Kinase Kinase 4; JNK Mitogen-Activated Protein Kinases; Isoenzymes; Lipopolysaccharides; Protein Kinase C; cdc42 GTP-Binding Protein; Type C Phospholipases; Signal Transduction; Cell Line; Mitogen-Activated Protein Kinase Kinases
Procyk, K., Rippo, M., Testi, R., Hofmann, F., Parker, P., Baccarini, M. (2000). Lipopolysaccharide induces jun N-terminal kinase activation in macrophages by a novel Cdc42/Rac-independent pathway involving sequential activation of protein kinase C zeta and phosphatidylcholine-dependent phospholipase C. BLOOD, 96(7), 2592-2598.
Procyk, K; Rippo, M; Testi, R; Hofmann, F; Parker, P; Baccarini, M
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/62736
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