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
Copyright
Copyright 2010, all rights reserved. This open access ETD is published by Wright State University and OhioLINK.
