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

Autor(en)

Katarzyna J. Procyk, Maria Rita Rippo, Roberto Testi, Frederike Hofmann, Peter J. Parker, Manuela Baccarini

Abstrakt

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) ? 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 PKC? 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. (C) 2000 by The American Society of Hematology.

Organisation(en)

Externe Organisation(en)

Cancer Research UK, Università Politecnica delle Marche, Fondazione Santa Lucia, King's College London

Journal

Blood

Band

96

Seiten

2592-2598

Anzahl der Seiten

7

ISSN

0006-4971

Publikationsdatum

2000

Peer-reviewed

Ja

ÖFOS 2012

1060 Biologie

Link zum Portal

https://ucrisportal.univie.ac.at/de/publications/lipopolysaccharide-induces-jun-nterminal-kinase-activation-in-macrophages-by-a-novel-cdc42racindependent-pathway-involving-sequential-activation-of-protein-kinase-c--and-phosphatidylcholinedependent-phospholipase-c(fb3c7fb2-de4a-4a30-9221-78af9f9b387a).html