Interactions between proteins and phosphoinositides can affect subcellular localization, protein-protein interactions, enzymatic activity, and downstream signaling events in a spatially and temporally controlled manner. Intracellular phosphoinositide levels are tightly controlled by specific kinases and phosphatases, and the importance of this regulation is reflected by their association with several human diseases, including cancer, acute myeloid leukemia, diabetes, X-linked myotubular myopathy, Charcot-Marie-Tooth disease, and Lowe syndrome. The focus of this project is to determine the functional role of pleckstrin homology domain-mediated phosphoinositide binding of human DIP13alpha and DIP13beta proteins, which are involved in cell proliferation, G2/M cell cycle regulation, modulation of AKT activity, and apoptosis.
The first aim i s to further characterize DIP13alpha and DIP13beta phosphoinositide binding specificity and affinity in vitro.
The second aim i s to determine whether PH domain-mediated phosphoinositide binding by DIP13 proteins contributes to their membrane-associated subcellular localization and protein-protein interactions.
The third aim i s to determine whether phosphoinositide binding contributes to the biological functions of DIP13alpha and DIP13beta.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32CA108196-01A1
Application #
6887100
Study Section
Special Emphasis Panel (ZRG1-F05 (20))
Program Officer
Lohrey, Nancy
Project Start
2005-02-01
Project End
2008-01-31
Budget Start
2005-02-01
Budget End
2006-01-31
Support Year
1
Fiscal Year
2005
Total Cost
$55,352
Indirect Cost
Name
Wake Forest University Health Sciences
Department
Biology
Type
Schools of Medicine
DUNS #
937727907
City
Winston-Salem
State
NC
Country
United States
Zip Code
27157