Research focus

The a-helical bundle cytokine family comprises most interleukins, the interferons and colony stimulating factors, together with hormones such as growth hormone and leptin. They control many levels of intercellular communication involved in development, host defense and metabolism in higher eukaryotes. Several human diseases are associated with malfunctioning of this communication system. Their receptors are composed of an extracellular, ligand-binding part that is linked to the cytosolic, signaling domain by a single transmembrane region. We are investigating several key aspects of these receptors. Detailed studies are ongoing to understand the molecular mechanisms that underlie receptor activation upon ligand binding. We focus here on the leptin receptor, and from these insights several leptin antagonists were developed. A key signaling event downstream of these receptors is activation of the JAK/STAT pathway, and our MAPPIT two-hybrid toolbox is based on this signaling route. Using MAPPIT and other technologies including molecular modeling, we investigate several protein interactions that are important in the innate immune response.