Our major research focus is on the characterization of the IL-6 receptor and its signal transduction components. We have obtained biochemical and functional evidence for the cell-surface expression of a third component of the IL-6 receptor besides the known alpha and beta chain. This novel IL-6 binding protein (p145) appears to be essential for high-affinity IL-6 binding and its expression correlated with IL-6 responsiveness. Attempts were made to generate monoclonal antibodies against p145 in order to further characterize it on a molecular level. Furthermore, we are currently investigating the involvement of a putative tyrosine kinase as part of the IL-6 signal transducing unit. Preliminary evidence indicates that IL-6 activates a kinase activity in certain IL-6 responsive human cell lines. Studies are underway to biochemically characterize this kinase. In a third line of studies, we are currently attempting to express the human IL-6 receptor alpha and beta chains in Xenopus laevis oocytes. This system should provide us with a highly valuable experimental model system to study the structural requirements of a functional human IL-6 receptor. Our ultimate goal is to understand the physiological and pathological role of IL-6 in human health and disease.
