Bacterial lipopolysaccharide (LPS), the major structural component of the o
uter wall of Gram-negative bacteria, is a potent initiator of an inflammato
ry response and serves as an indicator of bacterial infection. Although CD1
4 has been identified as the main LPS receptor, accumulating evidence has s
uggested the possible existence of other functional receptor(s). In this st
udy, using affinity chromatography, peptide mass fingerprinting and fluores
cence resonance energy transfer, we have identified four new proteins that
form an activation cluster after LPS ligation and are involved in LPS signa
l transduction. Here we present evidence that implicates heat shock protein
s 70 and 90, chemokine receptor 4 and growth differentiation factor 5 as th
e main mediators of activation by bacterial lipopolysaccharide.