Deorphanization of the human leukocyte tyrosine kinase (LTK) receptor by a signaling screen of the extracellular proteome

Secreted factors and their cell-surface receptors play important roles in the communication between cells in normal and pathological conditions. There are many transmembrane receptor-like proteins whose ligands have not been identified (also known as orphan receptors). Knowledge of the ligand should help in understanding the biological role of the receptor. We used a strategy of screening the extracellular proteome, one protein at a time, to identify ligands for such receptors. We discovered the ligands for the orphan receptor leukocyte tyrosine kinase. To our knowledge, this is the first case in which secreted factor ligands were identified for an orphan receptor with this technique. This approach is especially valuable when little is known about the ligand.