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gp96 Leads the Way for Toll-like Receptors
Abstract
The role of the gp96 heat-shock protein in regulating Toll-like-receptor expression is incompletely understood. Yang et al. (2007) generated mice with conditional deficiency of gp96 in macrophages and found that this protein is an important chaperone for all Toll-like receptors that have been tested.
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The chaperone activity of gp96 is selective, with targets including integrins, TLRs, IGFs, thyroglobulin and the platelet glycoprotein Ib-IX-V complex.
“However, the chaperone activity of gp96 is selective, with targets including integrins, toll-like receptors (TLRs), insulin-like growth factors (IGFs), thyroglobulin and the platelet glycoprotein Ib-IX-V complex.2−8”
Gp96 is critical for proper folding and functional expression of a number of integrins and TLRs; in gp96-deficient cells, these proteins are minimally expressed at the cell surface as assessed by flow cytometry.
“Gp96 is critical for proper folding and functional expression of a number of integrins and TLRs; in gp96-deficient cells, these proteins are minimally expressed at the cell surface as assessed by flow cytometry.3,5”
The endoplasmic reticulum chaperone gp96 is required for the cell surface expression of a narrow range of proteins, including toll-like receptors (TLRs) and integrins.
“The endoplasmic reticulum chaperone gp96 is required for the cell surface expression of a narrow range of proteins, including toll-like receptors (TLRs) and integrins.”
The known gp96 clients, integrins and TLRs, fail to reach the cell surface in the absence of gp96 due to misfolding; it is therefore likely that LDLR family members are similarly affected in the absence of gp96.
“The known gp96 clients, integrins and TLRs, fail to reach the cell surface in the absence of gp96 due to misfolding1−8—it is therefore likely that LDLR family members are similarly affected in the absence of gp96.”
Citations
Cites
Roles of heat-shock proteins in innate and adaptive immunity.
Srivastava, P. (2002) · Nature reviews. Immunology · doi:10.1038/nri749 · Cited by 1,069
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Research works printed but not linked: 4
- Iwasaki, 2004, Nat. Immunol., 5, 987, 10.1038/ni1112 · DOI
- Randow, 2001, Nat. Cell Biol., 3, 891, 10.1038/ncb1001-891 · DOI · Paper page
- Warger, 2006, J. Biol. Chem., 281, 22545, 10.1074/jbc.M502900200 · DOI
- Yang, 2007, Immunity, 26, 215, 10.1016/j.immuni.2006.12.005 · DOI · Paper page
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Weekes, M. P., Antrobus, R., Talbot, S., Hör, S., Simecek, N., Smith, D. L., Bloor, S., Randow, F., & Lehner, P. J. (2012) · Journal of Proteome Research · doi:10.1021/pr201135e · Cited by 82
Metadata
- Authors
- Harding, C. V.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2007-02
- Volume
- 26
- Issue
- 2
- Pages
- 141-143
- ISSN
- 1074-7613
- Cited by
- 8
- References
- 1
- Language
- en
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