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

cAMP signaling and regulation by ph...

Laxman, Sunil.

Linked to FindBook

Google Book

Amazon

博客來

cAMP signaling and regulation by phosphodiesterases in trypanosomes.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	cAMP signaling and regulation by phosphodiesterases in trypanosomes./
Author:	Laxman, Sunil.
Description:	162 p.
Notes:	Adviser: Joseph A. Beavo.
Contained By:	Dissertation Abstracts International67-11B.
Subject:	Biology, Molecular. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3241917
ISBN:	9780542978906

cAMP signaling and regulation by phosphodiesterases in trypanosomes.
Laxman, Sunil.

cAMP signaling and regulation by phosphodiesterases in trypanosomes. - 162 p.

Adviser: Joseph A. Beavo.

Thesis (Ph.D.)--University of Washington, 2006.

Trypanosomes (T. brucei and T. cruzi) are unicellular, eukaryotic parasites causing major human diseases (sleeping sickness and Chagas disease respectively). The mechanism of cAMP signaling and regulation by phosphodiesterases is relatively unknown in these organisms. Both species appear to express two cAMP-specific Class I phosphodiesterases (PDEs) of the PDEB family. The first section of this study shows that the T. brucei TbrPDEB2 binds cAMP with high affinity and selectivity through its GAF-A domain. Additionally, binding of cAMP to the holoenzyme shows strong positive cooperativity. Point mutation of a key predicted binding site residue results in a complete loss of high affinity cAMP binding, and increases the apparent Km of the mutant enzyme for substrate, suggesting that cAMP binding to the GAF-A domain can regulate TbrPDEB2 by allowing the full activity of the enzyme to be expressed.

ISBN: 9780542978906Subjects--Topical Terms:

1017719
Biology, Molecular.

cAMP signaling and regulation by phosphodiesterases in trypanosomes.
LDR:03212nam 2200313 a 45 001 958509
005 20110704
008 110704s2006 eng d
020 $a 9780542978906
035 $a (UMI)AAI3241917
035 $a AAI3241917
040 $a UMI $c UMI
100 1 $a Laxman, Sunil. $3 1281970
245 1 0 $a cAMP signaling and regulation by phosphodiesterases in trypanosomes.
300 $a 162 p.
500 $a Adviser: Joseph A. Beavo.
500 $a Source: Dissertation Abstracts International, Volume: 67-11, Section: B, page: 6327.
502 $a Thesis (Ph.D.)--University of Washington, 2006.
520 $a Trypanosomes (T. brucei and T. cruzi) are unicellular, eukaryotic parasites causing major human diseases (sleeping sickness and Chagas disease respectively). The mechanism of cAMP signaling and regulation by phosphodiesterases is relatively unknown in these organisms. Both species appear to express two cAMP-specific Class I phosphodiesterases (PDEs) of the PDEB family. The first section of this study shows that the T. brucei TbrPDEB2 binds cAMP with high affinity and selectivity through its GAF-A domain. Additionally, binding of cAMP to the holoenzyme shows strong positive cooperativity. Point mutation of a key predicted binding site residue results in a complete loss of high affinity cAMP binding, and increases the apparent Km of the mutant enzyme for substrate, suggesting that cAMP binding to the GAF-A domain can regulate TbrPDEB2 by allowing the full activity of the enzyme to be expressed.
520 $a The second section of this study identifies and characterizes orthologs of the T. brucei PDEB family in T. cruzi (TcrPDEB1 and TcrPDEB2). These enzymes were also found to be cAMP specific, and resistant to mammalian PDE inhibitors. Both the T. cruzi and the T. brucei PDEB2s showed significant flagellar localization. The N-terminus+GAF A domains of TcrPDEBs also bound cAMP, with differences in their binding affinity and selectivity for cAMP and cGMP compared to TbrPDEB2. Fluorescent cAMP analogs were found to be substrates for TcrPDEB and TbrPDEB, opening the possibility of using MANT-cAMP in fluorescence based PDE assays for the study of trypanosomal PDEs.
520 $a In the third section of this study we reinvestigated a putative role of cAMP in trypanosome differentiation from proliferating long forms to non-dividing stumpy forms. Using cell membrane permeable analogs of cAMP, we showed that 5'AMP/adenosine analogs are potently anti-proliferative and cause the transformation of dividing bloodstream form trypanosomes into non-dividing stumpy forms. Non-hydrolyzable cAMP analogs do not cause this same effect. This data suggests that slender to stumpy transformation in trypanosomes may not be caused by cAMP, provides future directions in understanding the signal and mechanism for this transformation, and suggests the use of similar analogs as anti-trypanosomal drugs.
590 $a School code: 0250.
650 4 $a Biology, Molecular. $3 1017719
650 4 $a Chemistry, Biochemistry. $3 1017722
650 4 $a Health Sciences, Pharmacology. $3 1017717
690 $a 0307
690 $a 0419
690 $a 0487
710 2 0 $a University of Washington. $3 545923
773 0 $t Dissertation Abstracts International $g 67-11B.
790 $a 0250
790 1 0 $a Beavo, Joseph A., $e advisor
791 $a Ph.D.
792 $a 2006
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3241917