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Extracellular regulation of TGF-beta...
~
Cheng, Simon K.
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Extracellular regulation of TGF-beta signaling.
Record Type:
Electronic resources : Monograph/item
Title/Author:
Extracellular regulation of TGF-beta signaling./
Author:
Cheng, Simon K.
Description:
121 p.
Notes:
Source: Dissertation Abstracts International, Volume: 64-12, Section: B, page: 5883.
Contained By:
Dissertation Abstracts International64-12B.
Subject:
Biology, Cell. -
Online resource:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3114182
ISBN:
0496616758
Extracellular regulation of TGF-beta signaling.
Cheng, Simon K.
Extracellular regulation of TGF-beta signaling.
- 121 p.
Source: Dissertation Abstracts International, Volume: 64-12, Section: B, page: 5883.
Thesis (Ph.D.)--New York University, 2004.
The TGF-beta signals Nodal, Activin, Vg1/GDF1 and Lefty have been implicated in mesoderm induction and left-right patterning. Nodal and Activin both activate the Activin receptors, but only Nodal requires EGF-CFC co-receptors for signaling. I present biochemical and genetic evidence that Vg1 and GDF1 also depend on EGF-CFC proteins to bind to and signal through Activin receptors. In addition, I show that the TGF-beta signaling antagonist Lefty also acts through an EGF-CFC dependent mechanism, thereby inhibiting Nodal and Vg1 signaling, but not Activin signaling. Chimeric analysis between Activin and Nodal or Vg1 has identified a short sequence determinant that confers independence from EGF-CFC coreceptors and resistance to Lefty antagonists. My results suggest a more widespread requirement for coreceptors in the regulation of TGF-beta signaling. These Activin-like signaling pathways represent a remarkable example of how a simple signaling pathway consisting of ligand and receptors can be diversified by subtle sequence changes that modulate the interaction with coreceptors and their inhibitors. Furthermore, this work has led to novel insights into the roles of these genes during embryogenesis and tumor development.
ISBN: 0496616758Subjects--Topical Terms:
1017686
Biology, Cell.
Extracellular regulation of TGF-beta signaling.
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Source: Dissertation Abstracts International, Volume: 64-12, Section: B, page: 5883.
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Thesis (Ph.D.)--New York University, 2004.
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The TGF-beta signals Nodal, Activin, Vg1/GDF1 and Lefty have been implicated in mesoderm induction and left-right patterning. Nodal and Activin both activate the Activin receptors, but only Nodal requires EGF-CFC co-receptors for signaling. I present biochemical and genetic evidence that Vg1 and GDF1 also depend on EGF-CFC proteins to bind to and signal through Activin receptors. In addition, I show that the TGF-beta signaling antagonist Lefty also acts through an EGF-CFC dependent mechanism, thereby inhibiting Nodal and Vg1 signaling, but not Activin signaling. Chimeric analysis between Activin and Nodal or Vg1 has identified a short sequence determinant that confers independence from EGF-CFC coreceptors and resistance to Lefty antagonists. My results suggest a more widespread requirement for coreceptors in the regulation of TGF-beta signaling. These Activin-like signaling pathways represent a remarkable example of how a simple signaling pathway consisting of ligand and receptors can be diversified by subtle sequence changes that modulate the interaction with coreceptors and their inhibitors. Furthermore, this work has led to novel insights into the roles of these genes during embryogenesis and tumor development.
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http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3114182
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