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.
| 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 |
