Heat-shock protein 70 and heat-shock protein 90 associate with Toll-like receptor 4 in response to bacterial lipopolysaccharide

2004 ◽  
Vol 32 (4) ◽  
pp. 636-639 ◽  
Author(s):  
M. Triantafilou ◽  
K. Triantafilou
Keyword(s):  
Heat Shock ◽  
Cell Surface ◽  
Heat Shock Protein ◽  
Heat Shock Protein 90 ◽  
Innate Immune ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Surface Receptors ◽  
Innate Recognition ◽  
Shock Proteins

Mammalian responses to bacterial LPS (lipopolysaccharide) from the outer membrane of Gram-negative bacteria can lead to an uncontrolled inflammatory response that can be deadly for the host. It has been shown that the innate immune system employs at least three cell surface receptors, CD14, TLR4 (Toll-like receptor 4) and MD-2, in order to recognize bacterial LPS. In our previous work we have found that Hsps (heat-shock proteins) are also involved in the innate recognition of bacterial products. Their presence on the cell surface, as well as their involvement in the innate recognition process, are poorly understood. In the present study we have investigated the association of TLR4 with Hsp70 and Hsp90 following LPS stimulation, both on the cell surface and intracellularly. Our results show that Hsp70 and Hsp90 form a cluster with TLR4 within lipid microdomains following LPS stimulation. In addition, Hsp70 and Hsp90 seem to be involved in TLR4/LPS trafficking and targeting to the Golgi apparatus, since upon LPS stimulation we found that both Hsps are targeted to the Golgi along with TLR4. The present study sheds new light into the involvement of Hsps in the innate immune response.

scholarly journals Evidence for a role of heat shock protein-90 in toll like receptor 4 mediated pain enhancement in rats

Neuroscience ◽  
2009 ◽  
Vol 164 (4) ◽  
pp. 1821-1832 ◽  
Author(s):  
M.R. Hutchinson ◽  
K.M. Ramos ◽  
L.C. Loram ◽  
J. Wieseler ◽  
P.W. Sholar ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 90 ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4

scholarly journals Detrimental Role of Heat Shock Protein 60&70 and Toll-like Receptor 4 in Skeletal Muscle Ischaemia In Vitro

2013 ◽  
Vol 57 (5) ◽  
pp. 77S
Author(s):  
Ali Navi ◽  
Rebekah Yu ◽  
Xu Shi-Wen ◽  
Sidney Shaw ◽  
George Hamilton ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 60 ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Muscle Ischaemia

The Significance of Heat-Shock Protein GP96 and its Receptors' CD91 and Toll-Like Receptor 4 Expression at the Maternal Foetal Interface

2013 ◽  
Vol 70 (1) ◽  
pp. 10-23 ◽  
Author(s):  
Tamara Gulic ◽  
Gordana Laskarin ◽  
Arnela Redzovic ◽  
Senija Eminović ◽  
Herman Haller ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Heat Shock Protein Gp96

scholarly journals C-terminal sequences of hsp70 and hsp90 as non-specific anchors for tetratricopeptide repeat (TPR) proteins

2009 ◽  
Vol 423 (3) ◽  
pp. 411-419 ◽  
Author(s):  
Andrew J. Ramsey ◽  
Lance C. Russell ◽  
Michael Chinkers
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Homo Sapiens ◽  
Heat Shock Protein 90 ◽  
Phage Library ◽  
Tetratricopeptide Repeat ◽  
Terminal Sequence ◽  
C Terminus ◽  
Multiple Copies ◽  
Shock Proteins

Steroid-hormone-receptor maturation is a multi-step process that involves several TPR (tetratricopeptide repeat) proteins that bind to the maturation complex via the C-termini of hsp70 (heat-shock protein 70) and hsp90 (heat-shock protein 90). We produced a random T7 peptide library to investigate the roles played by the C-termini of the two heat-shock proteins in the TPR–hsp interactions. Surprisingly, phages with the MEEVD sequence, found at the C-terminus of hsp90, were not recovered from our biopanning experiments. However, two groups of phages were isolated that bound relatively tightly to HsPP5 (Homo sapiens protein phosphatase 5) TPR. Multiple copies of phages with a C-terminal sequence of LFG were isolated. These phages bound specifically to the TPR domain of HsPP5, although mutation studies produced no evidence that they bound to the domain's hsp90-binding groove. However, the most abundant family obtained in the initial screen had an aspartate residue at the C-terminus. Two members of this family with a C-terminal sequence of VD appeared to bind with approximately the same affinity as the hsp90 C-12 control. A second generation pseudo-random phage library produced a large number of phages with an LD C-terminus. These sequences acted as hsp70 analogues and had relatively low affinities for hsp90-specific TPR domains. Unfortunately, we failed to identify residues near hsp90's C-terminus that impart binding specificity to individual hsp90–TPR interactions. The results suggest that the C-terminal sequences of hsp70 and hsp90 act primarily as non-specific anchors for TPR proteins.

Sign in / Sign up

Export Citation Format

Share Document