During my appointment, the main focus of my research was to investigate, structurally and biochemically, protein:protein interactions between SR protein kinases (SRPKs) and their substrates. Human SRPK1 has been linked to cell cycle progression and is differentially expressed in various types of cancer: leukemia, colon cancer, testicular cancer and pancreatic cancer. Substrates of SRPKs, SR proteins, are involved in pre-mRNA splicing in eukaryotic organisms. The activity of SR proteins is dependent upon their phosphorylation state dictated by SRPKs. Thus, the manner of SR protein activation by SRPKs is critical for the proper splicing and subsequent expression of genes. Aberrant splicing is also responsible for numerous diseases, including cancer.

Specifically, I have discovered that the mode in which SRPKs recognize their substrates is conserved from humans to yeast. SRPK1 displays a unique mechanism of phosphorylation through docking interactions that are vital to regulating the number to phosphorylation sites. I have found that this unique mechanism of phosphorylation and docking interaction is conserved from humans to yeast and may play a role in regulating SRPK phosphorylation in other organisms as well.

PUBLICATIONS (resulting from this training)

Aubol BE, Ungs L, Lukasiewicz R, Ghosh G, Adams JA. (2004) Chemical clamping allows for efficient phosphorylation of the RNA carrier protein Npl3. J Biol Chem. 279:30182-8.

Lukasiewicz R, Nolen B, Adams JA, Ghosh G. (2007) The RGG domain of Npl3p recruits Sky1p through docking interactions. J Mol Biol. 367:249-61.

Lukasiewicz R, Velazquez-Dones A, Hagopian J, Fu XD, Adams JA, Ghosh G. (2007) Structurally unique yeast and mammalian SR protein kinases catalyze evolutionarily conserved phosphorylation reactions. In Preparation.