Identifying Receptor-Ligand Pairs

Secreted proteins that interact with receptors on the cell surface control all sorts of biological processes and provide targets for therapeutic intervention. Lin et al . used a systematic approach to search for previously unknown ligand-receptor pairs. They produced recombinant proteins from genes that appeared to encode secreted proteins and then tested the proteins individually for effects in a range of in vitro assays. Having identified a new cytokine, interleukin 34 (IL-34), the authors then looked for binding to recombinant extracellular domains of about 1600 transmembrane proteins, which led to the detection of IL-34 binding to the colony-stimulating factor 1 (CSF-1) receptor. Biological effects of IL-34 mediated through the CSF-1 receptor were confirmed in further studies. Thus, the authors' approach can identify important regulatory proteins and their receptors. H. Lin, E. Lee, K. Hestir, C. Leo, M. Huang, E. Bosch, R. Halenbeck, G. Wu, A. Zhou, D. Behrens, D. Hollenbaugh, T. Linnemann, M. Qin, J. Wong, K. Chu, S. K. Doberstein, L. T. Williams, Discovery of a cytokine and its receptor by functional screening of the extracellular proteome. Science 320 , 807-811 (2008). [Abstract] [Full Text]