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

The protein phosphatase with EF-hand...

Ramulu, Pradeep Y.

Linked to FindBook

Google Book

Amazon

博客來

The protein phosphatase with EF-hand family: Biochemical characterization and targeted deletion in mice.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	The protein phosphatase with EF-hand family: Biochemical characterization and targeted deletion in mice./
Author:	Ramulu, Pradeep Y.
Description:	209 p.
Notes:	Adviser: Jeremy Nathans.
Contained By:	Dissertation Abstracts International63-03B.
Subject:	Biology, Genetics. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3046541
ISBN:	0493607315

The protein phosphatase with EF-hand family: Biochemical characterization and targeted deletion in mice.
Ramulu, Pradeep Y.

The protein phosphatase with EF-hand family: Biochemical characterization and targeted deletion in mice. - 209 p.

Adviser: Jeremy Nathans.

Thesis (Ph.D.)--The Johns Hopkins University, 2002.

The rdgC/PPEF family of serine/threonine protein phosphatases is distinguished by the presence of C-terminal EF-hands and by neuron-specific expression, including frequent expression in primary sensory neurons. Aside from <italic> Drosophila</italic>, in which mutations in the <italic>rdgC</italic> gene have been demonstrated to cause a light-dependent retinal degeneration due to overphosphorylation of rhodopsin, the functions of the PPEF family are not known. Here we use the <italic>C. elegans</italic> PPEF homolog, CePPEF, as a model for the biochemical characterization of the PPEF family, and undergo the targeted deletion of <italic>PPEF-1</italic> and <italic>PPEF-2</italic> in mouse to understand the function of the PPEF family in vertebrate biology. We demonstrate that CePPEF is N-terminally modified by myristate and palmitate and that it has functional calcium-binding EF-hands at their C-termini. We also show that CePPEF, like other members of the rdgC/PPEF family, is specific to the nervous system and is found in some primary sensory neurons. These primary sensory neurons include the ciliary chemosensory neurons AWB and AWC, and within these cells CePPEF is highly enriched in the sensory cilia. These results establish the first direct evidence for fatty acylation and calcium binding of a PPEF family member and they reveal a remarkable conservation of sensory neuron expression among the members of this distinctive family of protein phosphatases. Targeted deletion of <italic>PPEF-1</italic> and <italic> PPEF-2</italic> in mice demonstrates that PPEF function is not critical for the prevention of retinal degeneration in vertebrates. Moreover, rhodopsin dephosphorylation kinetics are normal in <italic>PPEF-1</italic>/<italic> PPEF-2</italic> double knockouts, suggesting that the PPEFs have a role other than rhodopsin dephosphorylation in vertebrates. The finding that PPEF-2, but not rdgC, has a consensus 14-3-3 binding domain and that PPEF-2 interacts with 14-3-3ζ <italic>in vivo</italic> suggests that PPEF-2 may have a novel role in vertebrate photoreceptors, or that rdgC has a second, unknown function in <italic>Drosophila</italic> photoreceptors which is shared by PPEF-2 and which is uniquely regulated in vertebrates by 14-3-3 association.

ISBN: 0493607315Subjects--Topical Terms:

1017730
Biology, Genetics.

The protein phosphatase with EF-hand family: Biochemical characterization and targeted deletion in mice.
LDR:03223nam 2200289 a 45 001 927702
005 20110425
008 110425s2002 eng d
020 $a 0493607315
035 $a (UnM)AAI3046541
035 $a AAI3046541
040 $a UnM $c UnM
100 1 $a Ramulu, Pradeep Y. $3 1251265
245 1 0 $a The protein phosphatase with EF-hand family: Biochemical characterization and targeted deletion in mice.
300 $a 209 p.
500 $a Adviser: Jeremy Nathans.
500 $a Source: Dissertation Abstracts International, Volume: 63-03, Section: B, page: 1200.
502 $a Thesis (Ph.D.)--The Johns Hopkins University, 2002.
520 $a The rdgC/PPEF family of serine/threonine protein phosphatases is distinguished by the presence of C-terminal EF-hands and by neuron-specific expression, including frequent expression in primary sensory neurons. Aside from <italic> Drosophila</italic>, in which mutations in the <italic>rdgC</italic> gene have been demonstrated to cause a light-dependent retinal degeneration due to overphosphorylation of rhodopsin, the functions of the PPEF family are not known. Here we use the <italic>C. elegans</italic> PPEF homolog, CePPEF, as a model for the biochemical characterization of the PPEF family, and undergo the targeted deletion of <italic>PPEF-1</italic> and <italic>PPEF-2</italic> in mouse to understand the function of the PPEF family in vertebrate biology. We demonstrate that CePPEF is N-terminally modified by myristate and palmitate and that it has functional calcium-binding EF-hands at their C-termini. We also show that CePPEF, like other members of the rdgC/PPEF family, is specific to the nervous system and is found in some primary sensory neurons. These primary sensory neurons include the ciliary chemosensory neurons AWB and AWC, and within these cells CePPEF is highly enriched in the sensory cilia. These results establish the first direct evidence for fatty acylation and calcium binding of a PPEF family member and they reveal a remarkable conservation of sensory neuron expression among the members of this distinctive family of protein phosphatases. Targeted deletion of <italic>PPEF-1</italic> and <italic> PPEF-2</italic> in mice demonstrates that PPEF function is not critical for the prevention of retinal degeneration in vertebrates. Moreover, rhodopsin dephosphorylation kinetics are normal in <italic>PPEF-1</italic>/<italic> PPEF-2</italic> double knockouts, suggesting that the PPEFs have a role other than rhodopsin dephosphorylation in vertebrates. The finding that PPEF-2, but not rdgC, has a consensus 14-3-3 binding domain and that PPEF-2 interacts with 14-3-3ζ <italic>in vivo</italic> suggests that PPEF-2 may have a novel role in vertebrate photoreceptors, or that rdgC has a second, unknown function in <italic>Drosophila</italic> photoreceptors which is shared by PPEF-2 and which is uniquely regulated in vertebrates by 14-3-3 association.
590 $a School code: 0098.
650 4 $a Biology, Genetics. $3 1017730
650 4 $a Biology, Molecular. $3 1017719
650 4 $a Biology, Neuroscience. $3 1017680
690 $a 0307
690 $a 0317
690 $a 0369
710 2 0 $a The Johns Hopkins University. $3 1017431
773 0 $t Dissertation Abstracts International $g 63-03B.
790 $a 0098
790 1 0 $a Nathans, Jeremy, $e advisor
791 $a Ph.D.
792 $a 2002
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3046541