No description available.

Thesis--Wisconsin. / Vita. Includes bibliographical references.

Every cell is faced continuously with the task of transducing a vast number of external signals into appropriate intracellular responses. In mammalian cells, membrane bound receptors modulate the production of secondary messenger molecules, such as cyclic AMP (cAMP). Cell signaling through second messengers relies on the diffusion of such second messengers from sites of production to sites of intracellular action to modulate the activities of an intracellular effector molecule, which in turn modulates a cellular response. Protein kinase A is the primary sensor of intracellular concentrations of cAMP, and protein kinase A (PKA)-mediated phosphorylation events are regulated by fluctuations in cAMP concentrations. This thesis examines the mechanism by which protein kinase A functions within fish melanophore to regulate intracellular activities in response to cAMP. A novel in situ assay to monitor protein kinase A-dependent phosphorylation is described here. By using a fluorescent substrate, the activities of protein kinase A are characterized in living cells as a function of phosphorylation-dependent fluorescence decay. Physiologically manipulated cells were microinjected with the fluorescent substrate to correlate the activities of protein kinase A and the subsequent effects on melanosome distribution. Cytoplasmic compartmentalization of protein kinase A is one means to regulate the specificity of a multifunctional kinase. The physiologic effects of an overexpressed PKA anchoring protein, Ht31, demonstrated that protein kinase A anchoring is required to direct the movements of melanosomes. Additional studies demonstrated that protein kinase A redistributes with the stimulated movements of melanosomes and interacts with proteins from a motor-protein complex. These observations shed light on how a transduction complex, consisting of a group of proteins, which localize components within the cell and provide motor activity, is able to integrate signaling information that regulate melanosome movements. I propose a model and suggest that protein kinase A is a component of the transduction complex: the proposed PKA complex constitutes a molecular servomechanism comprised of a sensor, an effector, and a regulator that function together in feedback loop to direct the motor-protein dependent transport of melanosomes. / Graduation date: 2001

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Thesis (Ph.D.)--Ohio University, August, 2005. / Includes bibliographical references (leaves 130-156)

Thesis (Ph. D.)--University of Texas at Austin, 2004. / Supervisor: George Georgiou. Vita. Includes bibliographical references. Also available from UMI.

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