東華大學圖書館 |

Language: English

Help

回圖書館首頁

手機版館藏查詢

Back

Switch To: Labeled | MARC Mode | ISBD

FcepsilonRI ubiquitylation negativel...

Billingsley, James Michael.

Linked to FindBook

Google Book

Amazon

博客來

FcepsilonRI ubiquitylation negatively regulates receptor tyrosine phosphorylation and mast cell effector function.

Record Type:	Electronic resources : Monograph/item
Title/Author:	FcepsilonRI ubiquitylation negatively regulates receptor tyrosine phosphorylation and mast cell effector function./
Author:	Billingsley, James Michael.
Description:	108 p.
Notes:	Source: Dissertation Abstracts International, Volume: 67-02, Section: B, page: 0793.
Contained By:	Dissertation Abstracts International67-02B.
Subject:	Biology, Molecular. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3205890
ISBN:	9780542544408

FcepsilonRI ubiquitylation negatively regulates receptor tyrosine phosphorylation and mast cell effector function.
Billingsley, James Michael.

FcepsilonRI ubiquitylation negatively regulates receptor tyrosine phosphorylation and mast cell effector function. - 108 p.

Source: Dissertation Abstracts International, Volume: 67-02, Section: B, page: 0793.

Thesis (Ph.D.)--Harvard University, 2006.

The high-affinity IgE receptor, FcepsilonRI is a tetrameric immune receptor expressed on mast cells. Upon receptor aggregation, FcepsilonRI beta and gamma subunits are phosphorylated and ubiquitylated. Receptor phosphorylation functions to recruit and activate signaling complexes leading to the activation of effector responses. Ubiquitylation of components of signaling complexes negatively regulates cell activation; however, the specific function of FcepsilonRI ubiquitylation has not been characterized. Whether or not ubiquitylation of immune receptors regulates cell activation, as has been demonstrated for receptor tyrosine kinases, is unknown.

ISBN: 9780542544408Subjects--Topical Terms:

1017719
Biology, Molecular.

FcepsilonRI ubiquitylation negatively regulates receptor tyrosine phosphorylation and mast cell effector function.
LDR:03658nmm 2200313 4500 001 1828995
005 20071106080058.5
008 130610s2006 eng d
020 $a 9780542544408
035 $a (UMI)AAI3205890
035 $a AAI3205890
040 $a UMI $c UMI
100 1 $a Billingsley, James Michael. $3 1917869
245 1 0 $a FcepsilonRI ubiquitylation negatively regulates receptor tyrosine phosphorylation and mast cell effector function.
300 $a 108 p.
500 $a Source: Dissertation Abstracts International, Volume: 67-02, Section: B, page: 0793.
500 $a Adviser: Jean-Pierre Kinet.
502 $a Thesis (Ph.D.)--Harvard University, 2006.
520 $a The high-affinity IgE receptor, FcepsilonRI is a tetrameric immune receptor expressed on mast cells. Upon receptor aggregation, FcepsilonRI beta and gamma subunits are phosphorylated and ubiquitylated. Receptor phosphorylation functions to recruit and activate signaling complexes leading to the activation of effector responses. Ubiquitylation of components of signaling complexes negatively regulates cell activation; however, the specific function of FcepsilonRI ubiquitylation has not been characterized. Whether or not ubiquitylation of immune receptors regulates cell activation, as has been demonstrated for receptor tyrosine kinases, is unknown.
520 $a To specifically analyze the function of FcepsilonRI ubiquitylation, we engineered lysine-to-argine amino-acid substitutions in the cytoplasmic domains of FcepsilonRI gamma and beta subunits, to block the capacity of the proteins to be ubiquitylated. Ubiquitylation-incompetent FcepsilonRI subunits were expressed in U937 cells. K-R mutant FcepsilonRI are expressed on the cell surface at levels similar to wild-type FcepsilonRl and can function to activate signals leading to calcium mobilization. K-R substitution abrogates receptor ubiquitylation. K-R substitution mediates enhanced FcepsilonRI tyrosine phosphorylation upon receptor aggregation, but does not mediate enhanced calcium mobilization.
520 $a To further characterize the function of FcepsilonRI ubiquitylation. K-R mutant FcRbeta and FcRgamma components were expressed in FCRbeta-deficient and FcRgamma-deficient BMMC respectively. Consistent with the U937 model, K-R FcRbeta mediates enhanced FcepsilonRI tyrosine phosphorylation. K-R FcRbeta also mediates enhanced cytokine release and degranulation. By contrast, K-R mutant FcRgamma mediates impaired effector responses. We suggest that K-R substitution in FcRgamma impairs the ability of PKCdelta to phosphorylate a threonine residue in the FcRgamma ITAM. This modification, in conjunction with tyrosine phosphorylation, is required for syk activation. To bypass this requirement, we substituted the ITAM threonine residue with an aspartate residue to mimic the acidic phospho-threonine. This substitution was introduced to both the K-R and wild-type FcRgamma proteins. K-R,T-D FcRgamma mediates enhanced FcepsilonRI tyrosine phosphorylation, cytokine release and degranulation, similar to that observed with the K-R FcRbeta protein. In both the U937 and BMMC models, K-R substitution did not change the rate of receptor endocytosis.
520 $a These data are consistent with the hypothesis that ubiquitylation of components of immune receptors can negatively regulate receptor phosphorylation and down-stream effector responses.
590 $a School code: 0084.
650 4 $a Biology, Molecular. $3 1017719
650 4 $a Health Sciences, Immunology. $3 1017716
690 $a 0307
690 $a 0982
710 2 0 $a Harvard University. $3 528741
773 0 $t Dissertation Abstracts International $g 67-02B.
790 1 0 $a Kinet, Jean-Pierre, $e advisor
790 $a 0084
791 $a Ph.D.
792 $a 2006
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3205890