Publication Date

2010

Document Type

Thesis

Committee Members

Steven Berberich (Committee Member), Julian Gomez-cambronero (Committee Chair), Michael Leffak (Committee Member)

Degree Name

Master of Science (MS)

Abstract

Phospholipase D (PLD) is a crucial signaling enzyme involved in many cellular processes. The catalytic activity of PLD is essential for the production of Phosphatidic Acid (PA), a critical second messenger in cell signaling cascades downstream. Using the highly invasive rat mammary adenocarcinoma cell line mTLn3 as a metastatic model, we investigated the proficiency of these cells to invade using matrigels that mimic the basement membrane of the extracellular matrix (ECM), their activity through PLD enzymatic assays, as well as the potency of our potential inhibitors to inhibit PLD-mediated cell invasion and lipase activity. This study reveals that PLD-mediated cell invasion is dependent on protein-protein interactions with other cell signaling molecules such as Grb2 and Rac2 and their effect on lipase activity. Regulation of PLD2 activity by phosphorylation on tyrosine residue sites within its Phox domain are examined; in which we elucidate the effects of specific kinases EGFR, Jak3 and Src on cell invasion and enzymatic activity. Based off this approach, a therapeutic resolution will be proposed to diminish cell invasion in metastasis.

Page Count

101

Department or Program

Department of Biochemistry and Molecular Biology

Year Degree Awarded

2010


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