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Full-Text Articles in Life Sciences

Transforming Growth Factor-Beta Receptor Signalling Is Modulated By Integrin-Linked Kinase, Stellar H. Boo Nov 2013

Transforming Growth Factor-Beta Receptor Signalling Is Modulated By Integrin-Linked Kinase, Stellar H. Boo

Electronic Thesis and Dissertation Repository

Transforming growth factor-beta 1 (TGF-β1) modulates regeneration after injury through induction of fibroblast proliferation, migration, and differentiation into myofibroblasts. Induction of myofibroblast differentiation by TGF-β1 requires expression of integrin-linked kinase (ILK). I now show that ILK interacts with TGF-β receptor type II (TβRII) in primary dermal fibroblasts. Further, colocalization of ILK and TβRII can be observed at the cell membrane and in intracellular vesicles. The association of TβRII and ILK does not require TGF-β1 stimulation, kinase activity of TGF-β1 receptor type I or TβRII, and it does not involve interactions between ILK and focal adhesion-associated proteins. When this interaction is …


Analysis Of Subcellular Localization Patterns Suggest Non-Enzymatic Roles For Select Arogenate Dehydratases, Travis R. Howes Aug 2013

Analysis Of Subcellular Localization Patterns Suggest Non-Enzymatic Roles For Select Arogenate Dehydratases, Travis R. Howes

Electronic Thesis and Dissertation Repository

The final step of phenylalanine biosynthesis in planta is catalyzed by arogenate dehydratases (ADTs). Previously cloned ADT-CFP fusion genes were used to provide an in depth study of the subcellular localization of all six ADTs from Arabidopsis thaliana. Through co-localization of ADT-CFPs with a stroma-marker it is shown that most ADTs localize to stroma-filled projections from chloroplasts called stromules. The localization of ADT5 and ADT2 provide evidence for additional, non-enzymatic roles. In the case of ADT5, it is found to localize to the nucleus, suggestive of an uncharacterized nuclear role. The localization patterns of ADT2 are suggestive of a …


P2x7 Nucleotide Receptor Signaling In Osteoblasts, Matthew W. Grol Jul 2013

P2x7 Nucleotide Receptor Signaling In Osteoblasts, Matthew W. Grol

Electronic Thesis and Dissertation Repository

Nucleotides are released from cells of the osteoblast lineage in response to mechanical stimulation, and signal through two families of P2 nucleotide receptors – G protein-coupled P2Y receptors and ligand-gated P2X cation channels. Nearly every cell-type expresses multiple P2 receptor subtypes. However, the significance of these networks of receptors in any system is unclear. In this thesis, we demonstrate that the endogenous network of P2 receptors expressed by osteoblasts permits graded increases in Ca2+ signaling over a million-fold range of ATP concentrations. P2Y receptors mediate transient activation of the Ca2+/NFATc1 pathway, whereas stimulation of P2X7 causes sustained …


Amyloid Beta Resistance And The Warburg Effect: Re-Examining Alzheimer's Disease, Jordan Taylor Newington Jun 2013

Amyloid Beta Resistance And The Warburg Effect: Re-Examining Alzheimer's Disease, Jordan Taylor Newington

Electronic Thesis and Dissertation Repository

Alzheimer’s disease (AD) is characterized by deposition of the amyloid beta (Ab) peptide in the brain, an event which frequently but not universally correlates with nerve cell death. Although most nerve cells die in response to Ab, small populations of cells are able to survive by becoming resistant to Ab toxicity. Understanding the mechanisms by which cells become resistant to Ab may reveal novel treatments for AD. Interestingly, nerve cell lines selected for resistance against Ab exhibit increased glucose uptake and glycolytic flux. Here I show that these metabolic changes are mediated through an upregulation of pyruvate dehydrogenase kinase 1 …


Systematic Analysis Of Residues In Conserved Region 3 Of The Human Papillomavirus 16 E7 Oncoprotein, Biljana Todorovic May 2013

Systematic Analysis Of Residues In Conserved Region 3 Of The Human Papillomavirus 16 E7 Oncoprotein, Biljana Todorovic

Electronic Thesis and Dissertation Repository

Although remarkable biological diversity is exhibited by viruses, as obligate intracellular parasites, they rely on host cell functions. As such, viruses typically must overcome a set of host barriers that prevent infection. For human papillomaviruses (HPV) one of these barriers is the state of terminal differentiation of the host cell. For that purpose HPVs encode two major oncoproteins, E6 and E7, which combine their efforts to effectively uncouple cellular differentiation from the cell cycle arrest. The E7 proteins have no intrinsic enzymatic activity or DNA binding ability, but they bind and manipulate numerous host proteins. E7 is a modular oncoprotein …


Subcellular Analysis Of The Disulfide Proteome In P66shc Expressing Nerve Cells, Tyler Cann Jan 2013

Subcellular Analysis Of The Disulfide Proteome In P66shc Expressing Nerve Cells, Tyler Cann

Electronic Thesis and Dissertation Repository

The longevity associated protein p66Shc has been suggested to regulate organismal lifespan through initiation of apoptotic pathways. Following stress-induced translocation into the mitochondria, p66Shc promotes increased reactive oxygen species (ROS) production and triggers poorly defined downstream signaling events that lead to decreased cell viability. Protein disulfide bonding has recently emerged as aROSdependent post-translational modification that regulates protein function and signaling processes. Using the mouse hippocampal HT-22 cell line, I sought to determine the changes in the disulfide proteome associated with p66Shc mediatedROSproduction. Through Redox 2D-SDSPAGEanalysis of mitochondrial and cytosolic extracts, redox sensitive proteins altered by p66Shc mediatedROSformation were identified. Of …