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The K-Ras/microtubule connection.

Chen, Zhui.

The K-Ras/microtubule connection.

Record Type:	Electronic resources : Monograph/item
Title/Author:	The K-Ras/microtubule connection.
Author:	Chen, Zhui.
Description:	144 p.
Notes:	Source: Dissertation Abstracts International, Volume: 65-06, Section: B, page: 2917.
Notes:	Supervisor: Patrick J. Casey.
Contained By:	Dissertation Abstracts International65-06B.
Subject:	Chemistry, Biochemistry.
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3135125
ISBN:	0496823493

The K-Ras/microtubule connection.
Chen, Zhui.

The K-Ras/microtubule connection. - 144 p.

Source: Dissertation Abstracts International, Volume: 65-06, Section: B, page: 2917.

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

Further studies showed that K-Ras, but not H-Ras or N-Ras, is selectively activated by paclitaxel in an acute fashion. The small G protein Rac1 is also acutely activated in the same time range. Neither K-Ras nor Rac1 was activated by paclitaxel in Icmt null cells due to lack of interaction between K-Ras and microtubules. A dominant-negative protein, GFP-KnCVYM blocked the activation of K-Ras and Rac1 induced by paclitaxel but not by EGF. The paclitaxel-stimulated Rac1 activation was abolished in K-Ras deficient cells, and overexpression of GFP-K-Ras, but not GFP-H-Ras, restored this activation. These results for the first time demonstrated a specific K-Ras to Rac1 signaling process that is dependent on the interaction between K-Ras and microtubules. This microtubule-dependent K-Ras-to-Rac1 signaling may in part explain the functional difference between K-Ras and other isoforms of Ras proteins.

ISBN: 0496823493Subjects--Topical Terms:

226900
Chemistry, Biochemistry.

The K-Ras/microtubule connection.
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245 1 4 $a The K-Ras/microtubule connection.
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500 $a Source: Dissertation Abstracts International, Volume: 65-06, Section: B, page: 2917.
500 $a Supervisor: Patrick J. Casey.
502 $a Thesis (Ph.D.)--Duke University, 2003.
520 # $a Further studies showed that K-Ras, but not H-Ras or N-Ras, is selectively activated by paclitaxel in an acute fashion. The small G protein Rac1 is also acutely activated in the same time range. Neither K-Ras nor Rac1 was activated by paclitaxel in Icmt null cells due to lack of interaction between K-Ras and microtubules. A dominant-negative protein, GFP-KnCVYM blocked the activation of K-Ras and Rac1 induced by paclitaxel but not by EGF. The paclitaxel-stimulated Rac1 activation was abolished in K-Ras deficient cells, and overexpression of GFP-K-Ras, but not GFP-H-Ras, restored this activation. These results for the first time demonstrated a specific K-Ras to Rac1 signaling process that is dependent on the interaction between K-Ras and microtubules. This microtubule-dependent K-Ras-to-Rac1 signaling may in part explain the functional difference between K-Ras and other isoforms of Ras proteins.
520 # $a Ras-mediated signal transudation pathways play critical roles in the regulation of cellular proliferation and differentiation. Newly synthesized Ras proteins undergo a series of C-terminal posttranslational modifications in cytosol, including prenylation, proteolysis and methylation. A search for factors involved in the intracellular trafficking of Ras has identified a specific and prenylation-dependent interaction between tubulin/microtubules and K-Ras. In vitro analysis using chimeric proteins revealed that the polylysine region of K-Ras is required for its binding to microtubules. Removal of the three C-terminal amino acids of farnesylated K-Ras by proteolysis abolished its binding to microtubules, while methylation of the C-terminal prenylcysteine restored binding. Experiments in cells treated with a microtubule interfering agent, paclitaxel, confirmed these results.
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