TY - JOUR T1 - Casting a Wider Net: Whole Cell Assays to Capture Varied and Biased Signaling JF - Molecular Pharmacology JO - Mol Pharmacol DO - 10.1124/mol.112.081117 SP - mol.112.081117 AU - Terry Peter Kenakin Y1 - 2012/01/01 UR - http://molpharm.aspetjournals.org/content/early/2012/07/24/mol.112.081117.abstract N2 - The observation of complex receptor behaviors has shown how ligands can have multiple efficacies and also can differentially stimulate certain cellular signaling pathways over others (i.e. biased signaling). Conventional pharmacological assays (usually proximal to the receptor) will detect ligands that produce the signal defined by the assay (i.e. Ca2+, cyclic AMP etc.) but otherwise may miss biased ligands which produce little activation of pathways not measured by the assay. Theoretically this is less of a hazard for generic whole cell assays which may be sensitive to multiple signaling inputs. Whole cell assays have the advantage of detecting effects induced by a variety of receptor interactions with cytosolic proteins including those which may be previously unknown. These ideas are discussed within the context of the highthroughput flow cytometry measurement of receptor internalization described by Wu et al. (this issue). The internalization of receptors can be a useful therapeutic modality and the paper by Wu et al. illustrates how this new assay, targeted to downstream cellular effects, can uncover unique ligand efficacies linked to receptor internalization. ER -