Novel Signal Transduction Pathway Utilized by Extracellular HSP70

@article{Asea2002NovelST,
  title={Novel Signal Transduction Pathway Utilized by Extracellular HSP70},
  author={Alexzander A. A. Asea and Michael Rehli and Edith Kabingu and Jason A. Boch and Olivia Bar{\'e} and Philip E. Auron and Mary Ann Stevenson and Stuart K. Calderwood},
  journal={The Journal of Biological Chemistry},
  year={2002},
  volume={277},
  pages={15028 - 15034}
}
Recent studies have initiated a paradigm shift in the understanding of the function of heat shock proteins (HSP). It is now clear that HSP can and do exit mammalian cells, interact with cells of the immune system, and exert immunoregulatory effects. We recently demonstrated that exogenously added HSP70 possesses potent cytokine activity, with the ability to bind with high affinity to the plasma membrane, elicit a rapid intracellular Ca2+ flux, activate NF-κB, and up-regulate the expression of… Expand
Extracellular Hsp70 stimulates multiple signaling pathways in A431 carcinoma cells
TLDR
It is shown that Hsp70 stimulates TLR2/4 receptors in A431 squamous carcinoma cells and the neutralizing antibody to EGFR has no effect on the HSp70-induced EGFR activation, which suggests that neither extracellular Hsp 70 nor other extrace cellular factor binds to EG FR. Expand
Heat shock proteins and toll-like receptors.
  • A. Asea
  • Biology, Medicine
  • Handbook of experimental pharmacology
  • 2008
TLDR
This chapter discusses the most recent advances in the understanding of heat shock protein (HSP) and TLR interactions in general and highlights recent findings that demonstrate Hsp70 is a ligand for TLR and its biological significance. Expand
Stress proteins and initiation of immune response: chaperokine activity of hsp72.
  • A. Asea
  • Biology, Medicine
  • Exercise immunology review
  • 2005
TLDR
From its original description as solely an intracellular molecular chaperone, heat shock proteins have now been shown to function as initiators of the host's immune response; a process known as the chaperokine activity of Hsp70. Expand
Cytokine function of heat shock proteins.
  • M. Tsan, B. Gao
  • Medicine, Biology
  • American journal of physiology. Cell physiology
  • 2004
TLDR
It is essential that efforts should be directed to conclusively determine whether the reported HSP cytokine effects are due to HSPs or to contaminant(s) present in the HSP preparations before further exploring the implication and therapeutic potential of the putative cytokine function of H SPs. Expand
Mechanisms for Hsp70 secretion: crossing membranes without a leader.
TLDR
Following release of heat shock protein 70, it has been shown that Hsp70 binds to adjacent cells, suggesting that the secreted protein participates in paracrine or autocrine interactions with adjacent cell surfaces, suggesting the role for endolysosomes. Expand
Pathways of Hsp70 Release: Lessons from Cytokine Secretion
Heat shock proteins (HSP) have an essential role in the cytoplasm of all cells in mediating protein quality control. However, in addition to these molecular chaperone properties, HSP play additionalExpand
Dual Role of Heat Shock Proteins as Regulators of Apoptosis and Innate Immunity
TLDR
The roles of HSP70 and HSP90 in apoptosis and in innate immunity and how these functions are being exploited in cancer therapy are focused on. Expand
Novel heat shock protein Hsp70L1 activates dendritic cells and acts as a Th1 polarizing adjuvant.
TLDR
The ability of Hsp70L1 to activate DCs indicates its potential as a novel adjuvant for use with peptide immunizations; the Hsp 70L1 antigen peptide hybrid may serve as a more effective vaccine for the control of cancer and infectious diseases. Expand
Evolution of heat shock protein and immunity.
  • J. Robert
  • Biology, Medicine
  • Developmental and comparative immunology
  • 2003
TLDR
It has been proposed that, the role of hsps in immunity emerged early in evolution and to be widespread in extant organisms and data from studies with the frog Xenopus support this proposition. Expand
Investigating receptors for extracellular heat shock proteins.
TLDR
Methods for determining HSP receptors, approaches to study of individual receptors in cells that contain multiple such receptors, and methods for investigating HSP receptor function in vivo are discussed. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 43 REFERENCES
HSP70 stimulates cytokine production through a CD14-dependant pathway, demonstrating its dual role as a chaperone and cytokine
TLDR
Findings indicate that CD14 is a co-receptor for HSP70-mediated signaling in human monocytes and are indicative of an previously unrecognized function for H SP70 as an extracellular protein with regulatory effects on human monocyte, having a dual role as chaperone and cytokine. Expand
Heat shock protein 70 induced during tumor cell killing induces Th1 cytokines and targets immature dendritic cell precursors to enhance antigen uptake.
TLDR
Induction of hsp70 expression induces an infiltrate of T cells, macrophages, and predominantly dendritic cells (DCs) into the tumors as well as an intratumoral profile of Th1 cytokine expression and enhances immunogenicity via a T cell-mediated mechanism. Expand
Receptor-dependent mechanisms of cell stimulation by bacterial endotoxin.
TLDR
How LBP enables LPS binding to CD14 and how complexes of LPS and soluble or GPI-anchored CD14 participate in cell activation are discussed, and the evidence supporting a model for a functional LPS receptor of myeloid cells, which is multimeric, is reviewed. Expand
Cutting Edge: Heat Shock Protein 60 Is a Putative Endogenous Ligand of the Toll-Like Receptor-4 Complex1
TLDR
It is reported here that macrophages of C3H/HeJ mice, carrying a mutant Toll-like-receptor (Tlr) 4 are nonresponsive to hsp60, and this is the first report of a putative endogenous ligand of the Tlr4 complex. Expand
HSP70 peptide-bearing and peptide-negative preparations act as chaperokines
TLDR
Peptide-bearing and peptide-negative HSP70 preparations isolated from EMT6 mammary adenocarcinoma cells (EMT6-HSP70) act as chaperokines when admixed with murine splenocytes, suggesting that presence of peptide is not required for spontaneous activation of cells of the innate immune system. Expand
LPS‐binding proteins and receptors
TLDR
Various phenotypes of mice that lack genes encoding CD14, the scavenger receptor, and LBP are summarized to provide a means to develop and evaluate novel therapeutic approaches to the control of endotoxin shock. Expand
MyD88: an adapter that recruits IRAK to the IL-1 receptor complex.
TLDR
MyD88 plays the same role in IL-1 signaling as TRADD and Tube do in TNF and Toll pathways, respectively: it couples a serine/threonine protein kinase to the receptor complex. Expand
The interleukin 1 receptor: ligand interactions and signal transduction.
  • P. Auron
  • Biology, Medicine
  • Cytokine & growth factor reviews
  • 1998
TLDR
At least half of the IL-1-dependent NF-kappaB activation is independent of IRAK and uses a novel pathway involving the recruitment of phosphatidylinositol 3-kinase (PI3K) to a distinct site within the cytoplasmic domain of theIL-1 receptor. Expand
MyD88 is an adaptor protein in the hToll/IL-1 receptor family signaling pathways.
TLDR
MyD88 is implicate as a general adaptor/regulator molecule for the Toll/IL-1R family of receptors for innate immunity and induces activation of NF-kappaB via the Pelle-like kinase IRAK and the TRAF6 protein, similar to IL- 1R-mediated NF- kappaB activation. Expand
Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function.
TLDR
It is demonstrated that MyD88 is a critical component in the signaling cascade that is mediated by IL-1 receptor as well as IL-18 receptor, and increases in interferon-gamma production and natural killer cell activity in response to IL- 18 are abrogated. Expand
...
1
2
3
4
5
...