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Regulation of casein kinase I&egr; i...

Tsai, I-Chun.

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Regulation of casein kinase I&egr; in non-canonical Wnt signaling.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Regulation of casein kinase I&egr; in non-canonical Wnt signaling./
Author:	Tsai, I-Chun.
Description:	163 p.
Notes:	Adviser: David Virshup.
Contained By:	Dissertation Abstracts International67-12B.
Subject:	Biology, Cell. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3247186

Regulation of casein kinase I&egr; in non-canonical Wnt signaling.
Tsai, I-Chun.

Regulation of casein kinase I&egr; in non-canonical Wnt signaling. - 163 p.

Adviser: David Virshup.

Thesis (Ph.D.)--The University of Utah, 2007.

Casein kinase I epsilon (CKIepsilon) and casein kinase I delta (CKIdelta) are members of the CKI serine/threonine protein kinase family. These two highly-related kinases are ubiquitously expressed in mammalian tissues and are implicated in multiple cellular processes, including Wnt signaling transduction, circadian rhythms and Hedgehog pathway. Due to the ability to induce axis duplication and to activate the TCF-dependent reporter, CKIepsilon and CKIdelta were first reported as positive regulators of the Wnt/beta-catenin pathway. Biochemical studies in our laboratory demonstrated that CKIepsilon could destabilize the beta-catenin destruction complex, leading to the accumulation of beta-catenin. However, CKIepsilon is not only involved in the Wnt/beta-catenin pathway but is also required for the convergent extension (CE) movements during Xenopus development. CE comprises the morphological polarization and cell migration, regulating the formation of the body axis in a beta-catenin independent manner. Downstream of Wnt, Frizzled (Fz) receptors and Dishevelled (Dvl/Dsh) protein, CE movements can be stimulated by the activation of small GTPases, including Rho and Rac, which facilitate cytoskeleton reorganization and activate the JNK pathway. Although CKIepsilon activity has been shown to be important for the regulation of CE movements, the molecular mechanism by which CKIepsilon regulates CE movements has not been addressed yet. In order to find additional roles of CKIepsilon in the Wnt signaling pathway, my study focuses on understanding how CKIepsilon regulates CE movements and the beta-catenin-independent Wnt pathway. The characterization of CKIdelta and CKIepsilon mutants demonstrates that CKIepsilon/delta participate in the control of convergent extension (CE) movements through a beta-catenin independent mechanism. Further investigation of CKIepsilon function uncovered a novel mechanism of CKIepsilon, in which CKIepsilon activates Rap1, a monomeric GTP binding protein, through regulating the activity of a GAP (GTPase activating protein) of Rap1, E6TP1. Taken together, this dissertation extends the knowledge of CKIepsilon/delta in mediating Wnt/PCP (Planer Cell Polarity) signaling. Since the regulation of cell polarity is highly related to the regulation of cell migration and cancer metastasis, results from these studies not only deepen our understanding the CKIepsilon/delta function in embryonic development but also may be applied for understanding of the progression of cancer development in the future.Subjects--Topical Terms:

1017686
Biology, Cell.

Regulation of casein kinase I&egr; in non-canonical Wnt signaling.
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035 $a (UMI)AAI3247186
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100 1 $a Tsai, I-Chun. $3 1287185
245 1 0 $a Regulation of casein kinase I&egr; in non-canonical Wnt signaling.
300 $a 163 p.
500 $a Adviser: David Virshup.
500 $a Source: Dissertation Abstracts International, Volume: 67-12, Section: B, page: 7018.
502 $a Thesis (Ph.D.)--The University of Utah, 2007.
520 $a Casein kinase I epsilon (CKIepsilon) and casein kinase I delta (CKIdelta) are members of the CKI serine/threonine protein kinase family. These two highly-related kinases are ubiquitously expressed in mammalian tissues and are implicated in multiple cellular processes, including Wnt signaling transduction, circadian rhythms and Hedgehog pathway. Due to the ability to induce axis duplication and to activate the TCF-dependent reporter, CKIepsilon and CKIdelta were first reported as positive regulators of the Wnt/beta-catenin pathway. Biochemical studies in our laboratory demonstrated that CKIepsilon could destabilize the beta-catenin destruction complex, leading to the accumulation of beta-catenin. However, CKIepsilon is not only involved in the Wnt/beta-catenin pathway but is also required for the convergent extension (CE) movements during Xenopus development. CE comprises the morphological polarization and cell migration, regulating the formation of the body axis in a beta-catenin independent manner. Downstream of Wnt, Frizzled (Fz) receptors and Dishevelled (Dvl/Dsh) protein, CE movements can be stimulated by the activation of small GTPases, including Rho and Rac, which facilitate cytoskeleton reorganization and activate the JNK pathway. Although CKIepsilon activity has been shown to be important for the regulation of CE movements, the molecular mechanism by which CKIepsilon regulates CE movements has not been addressed yet. In order to find additional roles of CKIepsilon in the Wnt signaling pathway, my study focuses on understanding how CKIepsilon regulates CE movements and the beta-catenin-independent Wnt pathway. The characterization of CKIdelta and CKIepsilon mutants demonstrates that CKIepsilon/delta participate in the control of convergent extension (CE) movements through a beta-catenin independent mechanism. Further investigation of CKIepsilon function uncovered a novel mechanism of CKIepsilon, in which CKIepsilon activates Rap1, a monomeric GTP binding protein, through regulating the activity of a GAP (GTPase activating protein) of Rap1, E6TP1. Taken together, this dissertation extends the knowledge of CKIepsilon/delta in mediating Wnt/PCP (Planer Cell Polarity) signaling. Since the regulation of cell polarity is highly related to the regulation of cell migration and cancer metastasis, results from these studies not only deepen our understanding the CKIepsilon/delta function in embryonic development but also may be applied for understanding of the progression of cancer development in the future.
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710 2 0 $a The University of Utah. $3 1017410
773 0 $t Dissertation Abstracts International $g 67-12B.
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856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3247186