Heterotrimeric G proteins physically associated with the lipopolysaccharide receptor CD14 modulate both in vivo and in vitro responses to lipopolysaccharide |
| |
Authors: | KR Solomon EA Kurt-Jones RA Saladino AM Stack IF Dunn M Ferretti D Golenbock GR Fleisher RW Finberg |
| |
Affiliation: | Infectious Disease Unit, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA. |
| |
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. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|