RGD Reference Report - Rac GTPase activity is essential for lipopolysaccharide signaling to extracellular signal-regulated kinase and p38 MAP kinase activation in rat-2 fibroblasts. - Rat Genome Database

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Rac GTPase activity is essential for lipopolysaccharide signaling to extracellular signal-regulated kinase and p38 MAP kinase activation in rat-2 fibroblasts.

Authors: Woo, CH  Kim, JH 
Citation: Woo CH and Kim JH, Mol Cells 2002 Jun 30;13(3):470-5.
RGD ID: 1299246
Pubmed: PMID:12132588   (View Abstract at PubMed)

Lipopolysaccharide (LPS) has potent proinflammatory properties by acting on many cell types. Recently, mitogen-activated protein kinases (MAPKs) including extracellular signal-regulated kinase (ERK), p38 kinase, and c-jun N-terminal kinase (JNK) were shown to be involved in signal transduction in response to LPS. However, the detailed mechanism of LPS-induced signaling in the cell, especially the role of the Rho family GTPases remains largely unknown. In the present study, we investigated the role of Rac1, a member of the Rho family GTPases, in the LPS-induced MAPKs activation in Rat-2 fibroblasts. Our results showed that LPS induced the activation of ERK and p38 MAP kinase in a Rac-dependent manner, suggesting a mediatory role of Rac1 in LPS signaling to MAPKs stimulation. We also observed that LPS caused a time-dependent activation of Rac1. In addition, our results have shown that pretreatment with herbimycin or wortmannin dramatically inhibited Rac1 activation induced by LPS. These suggest that tyrosine kinase(s) and phosphatidylinositol 3-kinase (PI 3-kinase) are possibly acting upstream of Rac1 in the LPS signaling to MAPKs.

Objects referenced in this article
Gene Mapk14 mitogen activated protein kinase 14 Rattus norvegicus
Gene Mapk3 mitogen activated protein kinase 3 Rattus norvegicus
Gene Rac1 Rac family small GTPase 1 Rattus norvegicus
Gene Tnf tumor necrosis factor Rattus norvegicus

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