Heterotrimeric G proteins physically associated with the lipopolysaccharide receptor CD14 modulate both in vivo and in vitro responses to lipopolysaccharide.

K R Solomon; E A Kurt-Jones; R A Saladino; A M Stack; I F Dunn; M Ferretti; D Golenbock; G R Fleisher; R W Finberg

doi:10.1172/JCI4317

First published December 1, 1998 - More info

Abstract

Septic shock induced by lipopolysaccharide (LPS) triggering of cytokine production from monocytes/macrophages is a major cause of morbidity and mortality. The major monocyte/macrophage LPS receptor is the glycosylphosphatidylinositol (GPI)-anchored glycoprotein CD14. Here we demonstrate that CD14 coimmunoprecipitates with Gi/Go heterotrimeric G proteins. Furthermore, we demonstrate that heterotrimeric G proteins specifically regulate CD14-mediated, LPS-induced mitogen-activated protein kinase (MAPK) activation and cytokine production in normal human monocytes and cultured cells. We report here that a G protein binding peptide protects rats from LPS-induced mortality, suggesting a functional linkage between a GPI-anchored receptor and the intracellular signaling molecules with which it is physically associated.

Heterotrimeric G proteins physically associated with the lipopolysaccharide receptor CD14 modulate both in vivo and in vitro responses to lipopolysaccharide.

K R Solomon, E A Kurt-Jones, R A Saladino, A M Stack, I F Dunn, M Ferretti, D Golenbock, G R Fleisher, and R W Finberg

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Heterotrimeric G proteins physically associated with the lipopolysaccharide receptor CD14 modulate both in vivo and in vitro responses to lipopolysaccharide.

K R Solomon, E A Kurt-Jones, R A Saladino, A M Stack, I F Dunn, M Ferretti, D Golenbock, G R Fleisher, and R W Finberg

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