%0 Journal Article %J Sci Signal %D 2008 %T Alternative wnt signaling is initiated by distinct receptors. %A van Amerongen, Renee %A Mikels, Amanda %A Nusse, Roel %C Howard Hughes Medical Institute, Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA. %P re9 %R 10.1126/scisignal.135re9 %V 1 %X An unanswered question in the field of signal transduction research is how different signaling pathways are activated with strict specificity in a temporally and spatially controlled manner. Because extracellular ligands and membrane receptors constitute the first signaling modalities for most pathways, selectivity in ligand-receptor binding likely dictates the outcome of downstream signaling events. Unfortunately, possible complexities underlying ligand-receptor interactions are often overlooked. Here, we discuss basic principles of signal transduction initiated at the cell membrane, with the Wnt pathway, which harbors a multitude of ligands and receptors, as an example.