? ? 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 DIP13( and DIP13(, which are involved in G2/M cell cycle regulation, modulation of AKT activity, and apoptosis.
The first aim i s to determine phosphoinositide binding specificity and affinity.
The second aim i s to identify membrane-associated subcellular localization of DIP13( and DIP13(.
The third aim i s to determine whether phosphoinositide binding contributes to known DIP13( and DIP13 functions.
The final aim tests the hypothesis that homo-oligomerization facilitates phosphoinositide binding. It is hoped that these studies will lead to an independent research program. ? ? ?
| Chial, Heidi J; Lenart, Peter; Chen, Yong Q (2010) APPL proteins FRET at the BAR: direct observation of APPL1 and APPL2 BAR domain-mediated interactions on cell membranes using FRET microscopy. PLoS One 5:e12471 |
| Chial, Heidi J; Wu, Ruping; Ustach, Carolyn V et al. (2008) Membrane targeting by APPL1 and APPL2: dynamic scaffolds that oligomerize and bind phosphoinositides. Traffic 9:215-29 |
