東華大學圖書館 |

語系: 繁體中文

說明(常見問題)

回圖書館首頁

手機版館藏查詢

登入

回首頁

切換: 標籤 | MARC模式 | ISBD

The role of cholesterol in signal tr...

Chen, Xu.

FindBook

Google Book

Amazon

博客來

The role of cholesterol in signal transduction.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	The role of cholesterol in signal transduction./
作者:	Chen, Xu.
面頁冊數:	167 p.
附註:	Source: Dissertation Abstracts International, Volume: 64-08, Section: B, page: 3617.
Contained By:	Dissertation Abstracts International64-08B.
標題:	Biology, Cell. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3099968

The role of cholesterol in signal transduction.
Chen, Xu.

The role of cholesterol in signal transduction. - 167 p.

Source: Dissertation Abstracts International, Volume: 64-08, Section: B, page: 3617.

Thesis (Ph.D.)--Weill Medical College of Cornell University, 2003.

Binding of proteins to the plasma membrane can be achieved with various membrane targeting motifs, including combinations of fatty acids, isoprenoids, and basic domains. The goals of this thesis are to investigate whether attachment of different membrane targeting motifs influences the signaling capacity of membrane-bound signal transduction proteins by directing the proteins to different membrane microdomains. C-Raf-1 was chosen as a model for a signaling protein that is activated when membrane-bound. Three different membrane targeting motifs from K-Ras, Fyn, and Src proteins were fused to the N or C terminus of Raf-1. The ability of the modified Rafs to initiate MAPK signaling was then investigated. All three modified Raf-1 constructs activated MAPK to nearly equivalent levels. The extent of localization of the Raf-1 constructs to membrane microdomains known as rafts did not correlate with the level of MAPK activation. Moreover, treatment of cells with the raft disrupting drug methyl-beta-cyclodextrin (MbetaCD) caused activation of MAPK to levels equivalent to those achieved with membrane-targeted Raf constructs. The use of pharmacological agents as well as dominant negative mutants revealed that MAPK activation by MbetaCD proceeds via a phosphoinositide 3-kinase-dependent mechanism and involved increased tyrosine phosphorylation of the p85 subunit of PI3 kinase.Subjects--Topical Terms:

1017686
Biology, Cell.

The role of cholesterol in signal transduction.
LDR:03530nmm 2200277 4500 001 1860791
005 20041108070325.5
008 130614s2003 eng d
035 $a (UnM)AAI3099968
035 $a AAI3099968
040 $a UnM $c UnM
100 1 $a Chen, Xu. $3 1275298
245 1 4 $a The role of cholesterol in signal transduction.
300 $a 167 p.
500 $a Source: Dissertation Abstracts International, Volume: 64-08, Section: B, page: 3617.
500 $a Adviser: Marilyn D. Resh.
502 $a Thesis (Ph.D.)--Weill Medical College of Cornell University, 2003.
520 $a Binding of proteins to the plasma membrane can be achieved with various membrane targeting motifs, including combinations of fatty acids, isoprenoids, and basic domains. The goals of this thesis are to investigate whether attachment of different membrane targeting motifs influences the signaling capacity of membrane-bound signal transduction proteins by directing the proteins to different membrane microdomains. C-Raf-1 was chosen as a model for a signaling protein that is activated when membrane-bound. Three different membrane targeting motifs from K-Ras, Fyn, and Src proteins were fused to the N or C terminus of Raf-1. The ability of the modified Rafs to initiate MAPK signaling was then investigated. All three modified Raf-1 constructs activated MAPK to nearly equivalent levels. The extent of localization of the Raf-1 constructs to membrane microdomains known as rafts did not correlate with the level of MAPK activation. Moreover, treatment of cells with the raft disrupting drug methyl-beta-cyclodextrin (MbetaCD) caused activation of MAPK to levels equivalent to those achieved with membrane-targeted Raf constructs. The use of pharmacological agents as well as dominant negative mutants revealed that MAPK activation by MbetaCD proceeds via a phosphoinositide 3-kinase-dependent mechanism and involved increased tyrosine phosphorylation of the p85 subunit of PI3 kinase.
520 $a In order to determine whether MbetaCD treatment induced tyrosine phosphorylation of other cellular proteins, pTyr Western blotting and immunostaining were performed. The results showed that cholesterol depletion with MbetaCD caused an increase in pTyr levels of a 180 kD protein which was identified as the EGF receptor (EGFR) using affinity purification and Mass spectrometry. Cross-linking experiments showed that MbetaCD induced dimerization of EGFR, indicative of receptor activation. Reagents that block release of membrane-bound EGFR ligands did not affect MbetaCD-induced tyrosine phosphorylation of EGFR, indicating that MbetaCD activation of EGFR is ligand independent. Moreover, MbetaCD treatment resulted in increased tyrosine phosphorylation of EGFR downstream targets and Ras activation. Incubation of cells with the specific EGFR inhibitor AG4178 blocked MbetaCD induced phosphorylation of EGFR, SHC, PLC gamma and Gab1, as well as MAPK activation. We conclude that cholesterol depletion from the plasma membrane by MbetaCD causes ligand-independent activation of EGFR, resulting in MAPK activation by PI3 Kinase and Ras dependent mechanisms. Moreover, these studies reveal a novel mode of action of MbetaCD, in addition to its ability to disrupt membrane rafts.
590 $a School code: 0967.
650 4 $a Biology, Cell. $3 1017686
650 4 $a Chemistry, Biochemistry. $3 1017722
690 $a 0379
690 $a 0487
710 2 0 $a Weill Medical College of Cornell University. $3 1021736
773 0 $t Dissertation Abstracts International $g 64-08B.
790 1 0 $a Resh, Marilyn D., $e advisor
790 $a 0967
791 $a Ph.D.
792 $a 2003
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3099968