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Full-Text Articles in Cell Biology

Role And Regulation Of The Actin-Regulatory Protein Hs1 In Tcr Signaling, Esteban Carrizosa Dec 2009

Role And Regulation Of The Actin-Regulatory Protein Hs1 In Tcr Signaling, Esteban Carrizosa

Publicly Accessible Penn Dissertations

Numerous aspects of T cell function, including TCR signaling, migration, and execution of effector functions, depend on the actin cytoskeleton. Cytoskeletal rearrangements are driven by the action of actin-regulatory proteins, which promote or antagonize the assembly of actin filaments in response to external cues. In this work, we have examined the regulation and function of HS1, a poorly-understood actin regulatory protein, in T cells. This protein, which becomes tyrosine phosphorylated upon T cell activation, is thought to function primarily by stabilizing existing branched actin filaments. Loss of HS1 results in unstable actin responses upon TCR engagement and defective Ca2+ responses ...


Mass Spectrometry-Based Proteomics Reveals Distinct Mechanisms Of Astrocyte Protein Secretion, Todd M. Greco Aug 2009

Mass Spectrometry-Based Proteomics Reveals Distinct Mechanisms Of Astrocyte Protein Secretion, Todd M. Greco

Publicly Accessible Penn Dissertations

The ability of astrocytes to secrete proteins subserves many of its known function, such as synapse formation during development and extracellular matrix remodeling after cellular injury. Protein secretion may also play an important, but less clear, role in the propagation of inflammatory responses and neurodegenerative disease pathogenesis. While potential astrocyte-secreted proteins may number in the thousands, known astrocyte-secreted proteins are less than 100. To address this fundamental deficiency, mass spectrometry-based proteomics and bioinformatic tools were utilized for global discovery, comparison, and quantification of astrocyte-secreted proteins. A primary mouse astrocyte cell culture model was used to generate a collection of astrocyte-secreted ...


A Systems Approach To Cellular Signal Transduction, Jeremy E. Purvis Aug 2009

A Systems Approach To Cellular Signal Transduction, Jeremy E. Purvis

Publicly Accessible Penn Dissertations

Vital cellular processes such as growth, gene expression, and homeostasis depend on the correct transmission of molecular signals within and between cells. The vast complexity of these molecular signaling networks has necessitated the use of mathematical methods to model, characterize, and predict cellular responses. The work presented in this dissertation shows how computational methods were used to elucidate two clinically-relevant cellular signaling responses: (i) phosphotyrosine signaling through the epidermal growth factor receptor (EGFR), a receptor tyrosine kinase that is commonly overexpressed or structurally altered in human cancers; and (ii) phosphoinositide and calcium signaling in human platelets---the key cellular mediators of ...


Changes In Oxygen Tension Rapidly And Reversibly Regulate Macrophage Nitric Oxide Production, Mary A. Robinson Aug 2009

Changes In Oxygen Tension Rapidly And Reversibly Regulate Macrophage Nitric Oxide Production, Mary A. Robinson

Publicly Accessible Penn Dissertations

Macrophage nitric oxide (NO) production and hypoxia coexist during wound healing, and have been implicated in the pathogenesis and pathophysiology of multiple disease states including sepsis and cancer. Macrophages stimulated with pathogen associated molecular patterns (PAMPs) produce NO via inducible nitric oxide synthase (iNOS) from molecular O2, L-arginine, and NADPH. The first aim of this research was to characterize the degree and duration of hypoxia which would limit NO production by PAMPs stimulated macrophages. The second aim was to identify the contributing mechanism(s). Using a novel forced convection cell culture system, we demonstrated that NO production was rapidly (within ...


Role Of The F-Bar Protein Hof1 In The Regulation Of Chitin Synthesis And Cytokinesis In Yeast, Jennifer Hansen Schreiter Jan 2009

Role Of The F-Bar Protein Hof1 In The Regulation Of Chitin Synthesis And Cytokinesis In Yeast, Jennifer Hansen Schreiter

Publicly Accessible Penn Dissertations

Remodeling of the plasma membrane and extracellular matrix (ECM) at discrete cellular locations plays important roles in various cellular processes including angiogenesis and cytokinesis. In the budding yeast Saccharomyces cerevisiae , membrane trafficking delivers enzymes essential for the synthesis of the cell-wall (yeast ECM) component chitin to the bud neck at different phases of the cell cycle. During early stages of budding, a Chs3-synthesized chitin ring is deposited at the base of the new bud that is required for bud-neck integrity and normal cell shape. During cytokinesis, actomyosin ring contraction is linked to the formation of a Chs2-synthesized chitinous disk to ...