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The role of the Abl-related gene (Ar...

Hernandez, Samuel E.

The role of the Abl-related gene (Arg) tyrosine kinase in the regulation of adhesion-dependent cellular morphogenesis.

Record Type:	Electronic resources : Monograph/item
Title/Author:	The role of the Abl-related gene (Arg) tyrosine kinase in the regulation of adhesion-dependent cellular morphogenesis.
Author:	Hernandez, Samuel E.
Description:	118 p.
Notes:	Director: Anthony J. Koleske.
Notes:	Source: Dissertation Abstracts International, Volume: 66-12, Section: B, page: 6454.
Contained By:	Dissertation Abstracts International66-12B.
Subject:	Biology, Molecular.
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3194661
ISBN:	9780542426926

The role of the Abl-related gene (Arg) tyrosine kinase in the regulation of adhesion-dependent cellular morphogenesis.
Hernandez, Samuel E.

The role of the Abl-related gene (Arg) tyrosine kinase in the regulation of adhesion-dependent cellular morphogenesis. - 118 p.

Director: Anthony J. Koleske.

Thesis (Ph.D.)--Yale University, 2005.

Abl family kinases, which include the mammalian Abl and Arg kinases, regulate neuronal morphogenesis in the developing metazoan brain. Abl family kinases direct changes in actin-dependent processes such as membrane ruffling, filopodial protrusion, and cell motility. However, the mechanisms by which increased Abl or Arg kinase activity promote cytoskeletal rearrangements are unclear.

ISBN: 9780542426926Subjects--Topical Terms:

226919
Biology, Molecular.

The role of the Abl-related gene (Arg) tyrosine kinase in the regulation of adhesion-dependent cellular morphogenesis.
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100 0 $a Hernandez, Samuel E. $3 245032
245 1 4 $a The role of the Abl-related gene (Arg) tyrosine kinase in the regulation of adhesion-dependent cellular morphogenesis.
300 $a 118 p.
500 $a Director: Anthony J. Koleske.
500 $a Source: Dissertation Abstracts International, Volume: 66-12, Section: B, page: 6454.
502 $a Thesis (Ph.D.)--Yale University, 2005.
520 # $a Abl family kinases, which include the mammalian Abl and Arg kinases, regulate neuronal morphogenesis in the developing metazoan brain. Abl family kinases direct changes in actin-dependent processes such as membrane ruffling, filopodial protrusion, and cell motility. However, the mechanisms by which increased Abl or Arg kinase activity promote cytoskeletal rearrangements are unclear.
520 # $a I find that engagement of adhesion receptors stimulates p190RhoGAP phosphorylation in wild type but not in arg-/- neurons and fibroblasts. I also show that Arg phosphorylation of pl90RhoGAP on Y1105 stimulates it to inhibit Rho. Phosphorylation by Arg also stimulates p190RhoGAP's ability to induce neuritic processes in neuroblastoma cells. These results suggest Arg mediates adhesion-dependent regulation of neuronal morphogenesis in the postnatal brain by phosphorylating p190RhoGAP.
520 # $a Rho family GTPases regulate the actin cytoskeleton. I show that the Rho inhibitor p190RhoGAP is an Arg substrate in vitro and in vivo. p190RhoGAP has reduced phosphotyrosine content in arg-/- mice brain as compared to wild-type (WT) mice brain, suggesting that it is an Arg substrate in the developing postnatal mouse brain. I used purified recombinant proteins to confirm that p190RhoGAP is a direct substrate for Arg in vitro. Using two-dimensional phosphopeptide mapping I have shown that Arg phosphorylates p190RhoGAP on tyrosine 1105.
520 # $a p190RhoGAP forms a complex with p120RasGAP in response to adhesion-dependent phosphorylation. In order to determine the molecular mechanism by which Arg activates p190RhoGAP I have studied the effect of complex formation both in vitro and in vivo. I found that association with p120RasGAP is not sufficient to activate p190RhoGAP in vitro. However, when a fragment of p120RasGAP that can inhibit binding of full-length p120RasGAP to p190RhoGAP is expressed in HEK293 cells Arg can no longer stimulate complex formation or p190RhoGAP-mediated inhibition of Rho. Additionally, the p120RasGAP fragment can also inhibit the Arg-dependent activation of p190RhoGAP observed in response to integrin receptor stimulation. These results indicate that adhesion-dependent Arg-mediated activation of p190RhoGAP occurs by stimulating complex formation with p120RasGAP. Arg-dependent complex formation may, in turn, alter p190RhoGAP's localization in cells.
590 $a School code: 0265.
650 # 0 $a Biology, Molecular. $3 226919
650 # 0 $a Chemistry, Biochemistry. $3 226900
650 # 0 $a Biology, Neuroscience. $3 226972
690 $a 0307
690 $a 0317
690 $a 0487
710 0 # $a Yale University. $3 212430
773 0 # $g 66-12B. $t Dissertation Abstracts International
790 $a 0265
790 1 0 $a Koleske, Anthony J., $e advisor
791 $a Ph.D.
792 $a 2005
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