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Signaling pathways of microbial product receptors Toll-like receptors and CD14.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Signaling pathways of microbial product receptors Toll-like receptors and CD14.
Author:	Yim, Ching Kin.
Description:	184 p.
Notes:	Adviser: Robert W. Finberg.
Notes:	Source: Dissertation Abstracts International, Volume: 64-05, Section: B, page: 2182.
Contained By:	Dissertation Abstracts International64-05B.
Subject:	Chemistry, Biochemistry.
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3091728
ISBN:	0496394371

Signaling pathways of microbial product receptors Toll-like receptors and CD14.
Yim, Ching Kin.

Signaling pathways of microbial product receptors Toll-like receptors and CD14. [electronic resource] - 184 p.

Adviser: Robert W. Finberg.

Thesis (Ph.D.)--Harvard University, 2003.

Toll-like receptors (TLRs) and CD14 are important mammalian receptors for microbial products such as lipopolysaccharide (LPS). TLRs are transmembrane proteins; the intracellular domain of TLRs are thought to generate the signals involved in the recognition of microbial products which comprise the innate immune response. TLRs signal by the association of their Toll/IL-1 receptor (TIR)-domain with other TIR-containing adaptors such as MyD88 and the formation of a complex of IL-I receptor associated kinases (IRAKs) and adaptor molecule TRAF6. These in turn stimulate other downstream pathways, in a manner analogous to that of the IL-1 receptor complex. Drug inhibition studies have established that some unknown tyrosine kinases are involved in the signaling process of TLR/CD14 ligands. This thesis project establishes that src-family kinases are the tyrosine kinases involved in the upstream signaling processes of TLR2 and CD14. It is shown here that src-kinase Fyn associates with both TLR2 and IRAK-1 and src-kinases associate with TRAF6 after TLR2 activation. In addition, the association of TLR2 and the p85 subunit of phosphatidylinositol 3-kinase is prevented by the src-kinase inhibitors PP1. The involvement of src-kinases in TLR and CD14 signaling is demonstrated by the fact that the in vitro kinase reaction of the TLR2 and CD14 signaling complexes are inhibited by src-kinase inhibitors, and that src-kinase and PI 3-kinase inhibitors selectively inhibit or enhance cytokine secretions from TLR ligands. The discovery of src-kinases as mediators of the signaling initiated by microbial products potentially open a new chapter on the understanding of the regulation of the mammalian innate immunity.

ISBN: 0496394371Subjects--Topical Terms:

226900
Chemistry, Biochemistry.

Signaling pathways of microbial product receptors Toll-like receptors and CD14.
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