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Kielin/chordin-like protein 1/KCP 1,...

Lin, Jingmei.

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Kielin/chordin-like protein 1/KCP 1, a novel extracellular regulator in the TGF-beta family signaling pathway.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Kielin/chordin-like protein 1/KCP 1, a novel extracellular regulator in the TGF-beta family signaling pathway./
Author:	Lin, Jingmei.
Description:	126 p.
Notes:	Chair: Gregory R. Dressler.
Contained By:	Dissertation Abstracts International65-06B.
Subject:	Biology, Cell. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3137878
ISBN:	9780496850488

Kielin/chordin-like protein 1/KCP 1, a novel extracellular regulator in the TGF-beta family signaling pathway.
Lin, Jingmei.

Kielin/chordin-like protein 1/KCP 1, a novel extracellular regulator in the TGF-beta family signaling pathway. - 126 p.

Chair: Gregory R. Dressler.

Thesis (Ph.D.)--University of Michigan, 2004.

The transforming growth factor beta (TGF-beta) family contains two subfamilies: the TGF-beta/Activin/Nodal subfamily and the bone morphogenetic protein (BMP)/growth and differentiation factor (GDF)/Mullerian inhibiting substance (MIS) subfamily. Extracellular regulators that modulate BMP and TGF-beta signaling include the cysteine rich (CR) domain proteins, such as Chordin and Short gastrulation, which are potent inhibitors of BMP and Dpp signaling, respectively. We have identified a new mammalian member of the CR domain family that is expressed in developing limb buds and kidney tubules. The protein contains 19 CR domains and is most similar to the Xenopus protein Kielin. Thus, we have called this new gene and its corresponding protein KCP1, for Kielin Chordin like protein 1. Our data demonstrate that extracellular KCP1 is a potent activator of BMP-dependent signaling and an inhibitor on Activin-A- and TGF-beta1-mediated signaling. KCP1 is able to interact with the TGF-beta family ligands, including BMP-7, TGF-beta1 and Activin-A. KCP1 facilitates BMP-7 binding to its corresponding type I receptor, BMPRIA, thus enhancing downstream signaling. The KCP1-null mice, which were generated, were used to study renal fibrosis and acute tubular necrosis. The preliminary data suggest that KCP1 plays a role in the processes of both renal fibrosis and renal regeneration, probably by modulating the TGF-beta ligands-mediated signaling. The results presented in this thesis broaden our understanding of how factors modulate TGF-beta superfamily signaling. They enhance our understanding of the processes of both development and diseases involved in the TGF-beta signaling pathway, and provide the therapeutic potential to treat related diseases.

ISBN: 9780496850488Subjects--Topical Terms:

1017686
Biology, Cell.

Kielin/chordin-like protein 1/KCP 1, a novel extracellular regulator in the TGF-beta family signaling pathway.
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020 $a 9780496850488
035 $a (UMI)AAI3137878
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100 1 $a Lin, Jingmei. $3 1270410
245 1 0 $a Kielin/chordin-like protein 1/KCP 1, a novel extracellular regulator in the TGF-beta family signaling pathway.
300 $a 126 p.
500 $a Chair: Gregory R. Dressler.
500 $a Source: Dissertation Abstracts International, Volume: 65-06, Section: B, page: 2780.
502 $a Thesis (Ph.D.)--University of Michigan, 2004.
520 $a The transforming growth factor beta (TGF-beta) family contains two subfamilies: the TGF-beta/Activin/Nodal subfamily and the bone morphogenetic protein (BMP)/growth and differentiation factor (GDF)/Mullerian inhibiting substance (MIS) subfamily. Extracellular regulators that modulate BMP and TGF-beta signaling include the cysteine rich (CR) domain proteins, such as Chordin and Short gastrulation, which are potent inhibitors of BMP and Dpp signaling, respectively. We have identified a new mammalian member of the CR domain family that is expressed in developing limb buds and kidney tubules. The protein contains 19 CR domains and is most similar to the Xenopus protein Kielin. Thus, we have called this new gene and its corresponding protein KCP1, for Kielin Chordin like protein 1. Our data demonstrate that extracellular KCP1 is a potent activator of BMP-dependent signaling and an inhibitor on Activin-A- and TGF-beta1-mediated signaling. KCP1 is able to interact with the TGF-beta family ligands, including BMP-7, TGF-beta1 and Activin-A. KCP1 facilitates BMP-7 binding to its corresponding type I receptor, BMPRIA, thus enhancing downstream signaling. The KCP1-null mice, which were generated, were used to study renal fibrosis and acute tubular necrosis. The preliminary data suggest that KCP1 plays a role in the processes of both renal fibrosis and renal regeneration, probably by modulating the TGF-beta ligands-mediated signaling. The results presented in this thesis broaden our understanding of how factors modulate TGF-beta superfamily signaling. They enhance our understanding of the processes of both development and diseases involved in the TGF-beta signaling pathway, and provide the therapeutic potential to treat related diseases.
590 $a School code: 0127.
650 4 $a Biology, Cell. $3 1017686
650 4 $a Biology, Molecular. $3 1017719
650 4 $a Health Sciences, Pathology. $3 1017854
690 $a 0307
690 $a 0379
690 $a 0571
710 2 $a University of Michigan. $3 777416
773 0 $t Dissertation Abstracts International $g 65-06B.
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790 1 0 $a Dressler, Gregory R., $e advisor
791 $a Ph.D.
792 $a 2004
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3137878