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The physiological and cellular funct...

Cheng, Alan.

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The physiological and cellular functions of PTP1B in obesity and cancer.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	The physiological and cellular functions of PTP1B in obesity and cancer./
作者:	Cheng, Alan.
面頁冊數:	165 p.
附註:	Source: Dissertation Abstracts International, Volume: 65-01, Section: B, page: 0202.
Contained By:	Dissertation Abstracts International65-01B.
標題:	Chemistry, Biochemistry. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=NQ88439
ISBN:	0612884392

The physiological and cellular functions of PTP1B in obesity and cancer.
Cheng, Alan.

The physiological and cellular functions of PTP1B in obesity and cancer. - 165 p.

Source: Dissertation Abstracts International, Volume: 65-01, Section: B, page: 0202.

Thesis (Ph.D.)--McGill University (Canada), 2003.

Protein tyrosine phosphatase 1B (PTP1B) is the prototype for the superfamily of protein tyrosine phosphatases, and has been implicated in multiple signaling pathways. Of particular interest, gene targeting studies in mice have established PTP1B as a critical physiological regulator of insulin signaling and PTP1B knockout mice are resistant to both diabetes and obesity. At the start of this thesis, the mechanism underlying the role of PTP1B in obesity was not completely understood. Furthermore, the importance of PTP1B in cellular and oncogenic signaling was not well established. My doctoral research has primarily been aimed at addressing these two broad questions. Using leptin deficient mice as a genetic model of obesity, I demonstrate that the absence of PTP1B can lead to decreased adiposity and increased metabolic rate. Specifically, I showed that PTP1B deficient mice display increased sensitivity towards the metabolic actions of the hormone leptin. Substrate trapping studies demonstrate that PTP1B dephosphorylates the JAK2 kinase within the leptin signaling pathway, and hypothalami from PTP1B deficient mice display increased leptin mediated STAT3 activation. My studies identify PTP1B as a critical regulator of body metabolism. In order to characterize the cellular role of PTP1B in oncogenic signaling, I generated fibroblast cell lines from PTP1B deficient mice. Although, PTP1B dephosphorylates multiple receptor tyrosine kinases, PTP1B deficient fibroblasts exhibit impaired growth factor mediated MAPK activation. I found that loss of PTP1B leads to decreased Src activation, increased p120RasGAP expression, and increased p62Dok phosphorylation in immortalized fibroblasts. Collectively this results in decreased Ras activity, and thus, MAPK activation. Hence, my findings point to a mechanism by which PTP1B can act as a positive regulator of Ras signaling downstream of receptor tyrosine kinases, and consequently offers an explanation as to why PTP1B knockout mice do not present an increased incidence of tumors.

ISBN: 0612884392Subjects--Topical Terms:

1017722
Chemistry, Biochemistry.

The physiological and cellular functions of PTP1B in obesity and cancer.
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