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Control of effector T cell metabolis...

Hernandez, Jeniffer B.

Control of effector T cell metabolism and regulatory T cell generation by the serine/threonine kinase DRAK2.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Control of effector T cell metabolism and regulatory T cell generation by the serine/threonine kinase DRAK2.
Author:	Hernandez, Jeniffer B.
Description:	193 p.
Notes:	Source: Dissertation Abstracts International, Volume: 72-08, Section: B, page: .
Notes:	Adviser: Craig M. Walsh.
Contained By:	Dissertation Abstracts International72-08B.
Subject:	Biology, Cell.
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3457274
ISBN:	9781124675336

Control of effector T cell metabolism and regulatory T cell generation by the serine/threonine kinase DRAK2.
Hernandez, Jeniffer B.

Control of effector T cell metabolism and regulatory T cell generation by the serine/threonine kinase DRAK2. - 193 p.

Source: Dissertation Abstracts International, Volume: 72-08, Section: B, page: .

Thesis (Ph.D.)--University of California, Irvine, 2011.

The immune system has evolved several mechanisms to prevent autoimmune diseases. Unfortunately, millions of Americans suffer from one of a variety of autoimmune diseases. Current treatments are based on general suppression of the immune system. However, each autoimmune disease differs in the immune cell-type causing destruction. Identifying the molecular differences within each cell-type of the immune system will lead to better drugs suited for the autoimmune disease in question. The aim of this dissertation is to understand the underlying mechanism of the defective survival of T cells deficient in DRAK2 (Death-Associated Protein Related Apoptotic Kinase 2). DRAK2 is a serine/threonine kinase belonging to the DAP (Death-Associated Protein) family of kinases. DRAK2 is most abundantly expressed in lymphoid organs and is one of only 31 genes with this unique expression pattern. Drak2-deficient T cells have an altered threshold for activation, resulting in their ability to respond to suboptimal stimulation. Mice deficient in DRAK2 are resistant to mouse models of T cell-specific autoimmune diseases.

ISBN: 9781124675336Subjects--Topical Terms:

226967
Biology, Cell.

Control of effector T cell metabolism and regulatory T cell generation by the serine/threonine kinase DRAK2.
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100 1 $a Hernandez, Jeniffer B. $3 531100
245 1 0 $a Control of effector T cell metabolism and regulatory T cell generation by the serine/threonine kinase DRAK2.
300 $a 193 p.
500 $a Source: Dissertation Abstracts International, Volume: 72-08, Section: B, page: .
500 $a Adviser: Craig M. Walsh.
502 $a Thesis (Ph.D.)--University of California, Irvine, 2011.
520 $a The immune system has evolved several mechanisms to prevent autoimmune diseases. Unfortunately, millions of Americans suffer from one of a variety of autoimmune diseases. Current treatments are based on general suppression of the immune system. However, each autoimmune disease differs in the immune cell-type causing destruction. Identifying the molecular differences within each cell-type of the immune system will lead to better drugs suited for the autoimmune disease in question. The aim of this dissertation is to understand the underlying mechanism of the defective survival of T cells deficient in DRAK2 (Death-Associated Protein Related Apoptotic Kinase 2). DRAK2 is a serine/threonine kinase belonging to the DAP (Death-Associated Protein) family of kinases. DRAK2 is most abundantly expressed in lymphoid organs and is one of only 31 genes with this unique expression pattern. Drak2-deficient T cells have an altered threshold for activation, resulting in their ability to respond to suboptimal stimulation. Mice deficient in DRAK2 are resistant to mouse models of T cell-specific autoimmune diseases.
520 $a This dissertation provides (a) a mechanism for the regulation of DRAK2 activity and (b) identifies the mechanism behind DRAK2's control on T cell survival. In Chapter 2 we show that DRAK2 kinase activity is regulated in a calcium-dependent manner and that Ser12 phosphorylation is necessary for optimal suppression of T cell activation by this kinase. In Chapter 3 we demonstrate that DRAK2 is selectively important for T cell survival. Drak2-/- T cells were more sensitive to an intrinsic form of apoptosis that was prevented by CD28 ligation and homeostatic cytokines. In addition, Drak2-/- mice regained susceptibility to the mouse model of multiple sclerosis by T cell-specific Bcl-xL expression. In Chapter 4 we show that DRAK2 dictates the fate of a naive T cells by regulating their metabolism. This occurs via amplification of the activity of p70S6K1, leading to enhanced glycolysis and effector T cell survival. In addition, we show that inhibition of the DRAK2/p70S6K1 signaling axis promotes the differential generation of regulatory T cells. Blockade of DRAK2, which is most highly expressed in lymphocytes, may offer an alternative and selective approach in the suppression of autoimmunity.
590 $a School code: 0030.
650 4 $a Biology, Cell. $3 226967
650 4 $a Health Sciences, Immunology. $3 226966
690 $a 0379
690 $a 0982
710 2 $a University of California, Irvine. $b Biological Sciences - Ph.D. $3 531101
773 0 $t Dissertation Abstracts International $g 72-08B.
790 1 0 $a Walsh, Craig M., $e advisor
790 1 0 $a Fruman, David A. $e committee member
790 1 0 $a Lane, Thomas E. $e committee member
790 $a 0030
791 $a Ph.D.
792 $a 2011
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3457274