Type

Text

Type

Dissertation

Advisor

Du, Guangwei | Joav Prives | Deborah A. Brown | Michael A. Frohman.

Date

2010-08-01

Keywords

Health Sciences, Pharmacology | actin reorganization, Lipid Signaling, phosphatidic acid, PIPKI

Department

Department of Molecular and Cellular Pharmacology

Language

en_US

Source

This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree.

Identifier

http://hdl.handle.net/11401/72651

Publisher

The Graduate School, Stony Brook University: Stony Brook, NY.

Format

application/pdf

Abstract

Production and breakdown of certain phosphoinositides plays key roles in a variety of cellular processes. Among these, phosphatidylinositol-4, 5-phosphate (PIP 2) is well known for its critical functions in membrane trafficking, cytoskeletal organization, and signal transduction. Type I phosphatidylinositol-4-phosphate 5-kinase (PIPKI) is the main enzyme responsible for the synthesis of PIP2. Although PIPKI activity is regulated by small G proteins and phosphatidic acid (PA), the contribution of these upstream regulators in actin cytoskeletal reorganization remains unclear. The binding region of some other PA-regulated proteins has been identified. From these, it appears that binding may either be direct or electrostatic in nature. I have identified basic residues in the proposed membrane-binding region of PIPKIΓ that are required for membrane translocation, actin reorganization, and stimulation by PA. I also demonstrate here that the direct binding of PIPKI to PA through these residues is required for these important functions.

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