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

Phosphoregulation of NEK3 Kinase in ...

Schulhaus, Katherine M.

Linked to FindBook

Google Book

Amazon

博客來

Phosphoregulation of NEK3 Kinase in the Pathogenesis of Human Breast Carcinoma.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Phosphoregulation of NEK3 Kinase in the Pathogenesis of Human Breast Carcinoma./
Author:	Schulhaus, Katherine M.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2017,
Description:	284 p.
Notes:	Source: Dissertation Abstracts International, Volume: 78-08(E), Section: B.
Contained By:	Dissertation Abstracts International78-08B(E).
Subject:	Molecular biology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10252716
ISBN:	9781369678888

Phosphoregulation of NEK3 Kinase in the Pathogenesis of Human Breast Carcinoma.
Schulhaus, Katherine M.

Phosphoregulation of NEK3 Kinase in the Pathogenesis of Human Breast Carcinoma. - Ann Arbor : ProQuest Dissertations & Theses, 2017 - 284 p.

Source: Dissertation Abstracts International, Volume: 78-08(E), Section: B.

Thesis (Ph.D.)--Northwestern University, 2017.

The polypeptide hormone prolactin (PRL) is increasingly recognized as contributing to the development and progression of human breast cancer. This is supported by epidemiologic studies that found women with high levels of serum PRL are at an increased risk for developing breast cancer. Activation of the prolactin receptor (PRLR) by PRL contributes to the growth, survival and motility of human breast cancer cells. PRL has been shown to act as a chemoattractant for breast cancer cells, accompanied by reorganization of the cytoskeleton. However, the molecular mechanisms by which PRL induces cytoskeletal rearrangement and regulates cell migration/invasion are not well defined. Therefore, elucidation of the downstream signaling pathways that contribute to PRL stimulated breast cancer cell motility and invasion is of great importance.

ISBN: 9781369678888Subjects--Topical Terms:

517296
Molecular biology.

Phosphoregulation of NEK3 Kinase in the Pathogenesis of Human Breast Carcinoma.
LDR:03418nmm a2200313 4500 001 2124066
005 20171023101707.5
008 180830s2017 ||||||||||||||||| ||eng d
020 $a 9781369678888
035 $a (MiAaPQ)AAI10252716
035 $a AAI10252716
040 $a MiAaPQ $c MiAaPQ
100 1 $a Schulhaus, Katherine M. $3 3286039
245 1 0 $a Phosphoregulation of NEK3 Kinase in the Pathogenesis of Human Breast Carcinoma.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2017
300 $a 284 p.
500 $a Source: Dissertation Abstracts International, Volume: 78-08(E), Section: B.
500 $a Adviser: Charles V. Clevenger.
502 $a Thesis (Ph.D.)--Northwestern University, 2017.
520 $a The polypeptide hormone prolactin (PRL) is increasingly recognized as contributing to the development and progression of human breast cancer. This is supported by epidemiologic studies that found women with high levels of serum PRL are at an increased risk for developing breast cancer. Activation of the prolactin receptor (PRLR) by PRL contributes to the growth, survival and motility of human breast cancer cells. PRL has been shown to act as a chemoattractant for breast cancer cells, accompanied by reorganization of the cytoskeleton. However, the molecular mechanisms by which PRL induces cytoskeletal rearrangement and regulates cell migration/invasion are not well defined. Therefore, elucidation of the downstream signaling pathways that contribute to PRL stimulated breast cancer cell motility and invasion is of great importance.
520 $a The PRL/PRLR complex activates multiple signaling pathways, including the serine/threonine kinase, NEK3 (NIMA-related kinase 3). In vitro studies have implicated a role for NEK3 in the regulation of breast cancer cell migration, invasion, and the actin cytoskeletal reorganization necessary for these processes. However, the specific mechanisms of NEK3 activation in response to PRL signaling have not been defined. In this work, a novel PRL-inducible regulatory phosphorylation site within the activation segment of NEK3, threonine-165 (Thr-165), was identified. Phosphorylation at NEK3 Thr-165 was found to be dependent on activation of the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway using both pharmacological inhibition and siRNA-mediated knockdown approaches. Strikingly, inhibition of phosphorylation at NEK3 Thr-165 by expression of a phospho-deficient mutant (NEK3-T165V) resulted in increased focal adhesion size, formation of zyxin-positive focal adhesions, and reorganization of the actin cytoskeleton into stress fibers. Concordantly, NEK3-T165V cells exhibited migratory defects. Additionally, the focal adhesion adaptor protein paxillin (PXN) was identified as a potential substrate of NEK3 and we show that NEK3 phosphorylates PXN at residue Thr-401 within the LIM2 domain. Furthermore, it was demonstrated that expression of a phospho-deficient PXN mutant (PXN-T401V) resulted in inhibition of cell migration. Together, these data support a modulatory role for phosphorylation at NEK3 Thr-165 in focal adhesion maturation and/or turnover to promote breast cancer cell migration.
590 $a School code: 0163.
650 4 $a Molecular biology. $3 517296
650 4 $a Endocrinology. $3 610914
650 4 $a Cellular biology. $3 3172791
690 $a 0307
690 $a 0409
690 $a 0379
710 2 $a Northwestern University. $b Driskill Graduate Training Program in Life Sciences. $3 3282984
773 0 $t Dissertation Abstracts International $g 78-08B(E).
790 $a 0163
791 $a Ph.D.
792 $a 2017
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10252716