The focus of my project is to characterize D-AKAP1 using several biophysical methods, cAMP-dependent kinase(PKA) is localized to subcellular compartments through association with AKAPs. D-AKAP1 is special because it can target both type I and type II isoforms of PKA. Depending on the splicing of D-AKAP1, it can target PKA either to the outer mitochondrial membrane or the endoplasmic reticulum. There is little knowledge available about the structure or function of D-AKAP1 in signaling. I plan to establish basic structural information about domain organization and dynamics of D-AKAP1, as well as characterize the interaction of D-AKAP1 and the R subunits of PKA. I shall measure the binding affinities of D-AKAP1 with the R subunits, to establish any preferrences or kinetic differences between RI and RII binding. This research will help provide an understanding of RI vs. RII regulated PKA activity and it's significance in the mitochondria and endoplasmic reticulum. Additionally, I intend to explore the function of D-AKAP1 further by examining the function of the two highly conserved RNA binding domains, which were discovered on D-AKAP1 by sequence homology. I shall determine the binding partners for these domains and clarify the biological significance of D-AKAP1 in cell signaling.
| Kinderman, Francis S; Kim, Choel; von Daake, Sventja et al. (2006) A dynamic mechanism for AKAP binding to RII isoforms of cAMP-dependent protein kinase. Mol Cell 24:397-408 |
