Recombinant production and characterization of the human mast cell tryptases gamma and delta

点击翻译按钮获取中文摘要

Tryptases are serine proteinases that are among the most abundant and specific proteins of mast cells. Four tryptases have been identified in man, but only tryptase α and β have been functionally and structurally well characterized, showing that β is a key mediator involved in both the disease-related ‘bad’ and the more recently discovered healthmaintaining ‘good’ functions of mast cells. In contrast, tryptase γ and δ have received little attention and have remained orphan in respect to their functions and their contributions to mast cell biology. In this project we have expressed human tryptase γ and δ and variants in yeast and mammalian cells, thereby making all human tryptases available in our lab. We are currently using these recombinant tryptases to study their enzymatic activity and regulation, to elucidate their structures and to generate tools for their detection and inhibition. We plan to employ these tools specifically to explore the distinguishing features of the membrane-bound tryptase γ and its contributions to the mediator actions of tryptases. We believe that understanding and separating the properties and functions of the individual tryptases is essential for the understanding of tryptases as a group and for therapeutic interventions using any tryptase as target.