Date of Completion

8-27-2013

Embargo Period

8-27-2018

Keywords

AKAP, PKC, Scaffold, Enzyme

Major Advisor

Kimberly Dodge-Kafka

Associate Advisor

Ann Cowan

Associate Advisor

Lixia Yue

Associate Advisor

Vladimir Rodionov

Associate Advisor

Kevin Claffey

Field of Study

Biomedical Science

Degree

Doctor of Philosophy

Open Access

Campus Access

Abstract

The effective relay of extracellular messages to intracellular targets is a basic prerequisite for life. Despite a myriad of signals from outside the cell, the information directing changes in cellular physiology and function is precisely transduced by a relatively small complement of second messengers. The exact mechanisms by which these signaling enzymes achieve the necessary specificity within the cellular milieu remain elusive, but aberrant signaling through these common pathways underlies the onset and progression of every known disease. Numerous studies, including my own work described here, support the anchoring hypothesis as an explanation to this puzzle. We argue that the intracellular environment is pieced together from a heterogeneous network of microenvironments, each poised to respond to common inputs in different ways. These microenvironments are organized by a family of scaffolding proteins known as A-Kinase-Anchoring Proteins (AKAPs), which sequester unique combinations of signaling enzymes with their molecular targets. My research characterizes a novel interaction between the ubiquitous enzyme Protein Kinase C and the scaffold AKAP7, which is subsequently used as a model to provide a theoretical and experimental framework for understanding how, with the help of scaffolding proteins, cells use common signaling enzymes to make specific decisions.

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