The research appears as the "Paper of the Week" in the November 26 issue of the Journal of Biological Chemistry, an American Society for Biochemistry and Molecular Biology journal.
PKCΘ is a key signaling molecule in a class of immune cells called T lymphocytes, or T cells. These cells recognize short amino acid chains, or antigens, that are displayed on the surface of antigen-presenting cells and initiate immune responses when activated by the antigens.
"PKCΘ is selectively recruited to the contact region between T cells and antigen-presenting cells where it interacts with several signaling molecules to induce activation signals essential for productive T cell activation," explains Dr. Will Somers, of Wyeth Research. "Inhibiting PKCΘ signal transduction results in defects in T cell activation and cytokine production."
Dr. Somers and his colleagues at Wyeth determined the three-dimensional structure of the catalytic domain of PKCΘ using x-ray crystallography. "This is the first structure of a PKC at atomic resolution," notes Dr. Somers. "Moreover, the structure reported here was solved in the presence of the high potency protein kinase inhibitor, staurosporine, revealing the structural basis of inhibitor binding."
Dr. Somers believes his results have the potential to aid in identifying selective inhibitors of kinase function that can act as therapeutics for diseases in which T cells are targeting native rather than foreign antigens. Inhibiting PKC in these cases would disable the T cells and halt the autoimmun
Contact: Nicole Kresge
American Society for Biochemistry and Molecular Biology