Signal Pathway Identification and Deconvolution

The CellKey™ System provides a universal assay that can monitor the activity of different classes of G-protein coupled receptors and tyrosine kinase receptors and also differentiate between their signaling mechanisms.

Upon detecting GPCR activation, the CellKey™ System generates unique CDS response profiles that reflect the signaling pathways used by the cells. The profiles are characteristic of Gs-, Gi- or Gq- GPCRs and can be used to identify the G-protein coupling mechanism of unknown or orphan GPCRs.

Supervised clustering of known or reference ligands can be used to generate the typical response profiles for Gs, Gq, and Gi GPCRs in the cell line of interest. Clustering involves analyzing the responses in a dot plot format so that multiple data points can be analyzed simultaneously. An important component of clustering is analyzing the data over time, as the kinetics of the reponse is very important.

The unique response profiles can also be used to deconvolute the pathway through which receptors transduce their signals. The CellKey™ System measures and analyzes downstream signaling events triggered by receptor activation. A panel of signal pathway modulators can then be applied, and monitoring their effects on the CellKey™ response profiles provides a more detailed interpretation of the mechanism of action of lead compounds.

Thus, the CellKey™ response profiles can be mined to gain new, otherwise unattainable knowledge of native signaling pathways used by unknown receptors, receptors in different cellular backgrounds, or even different ligands that target the same receptor. In addition, the CellKey™ System enables the study of receptor homo- or heterodimerization and captures the diversity of one ligand signaling against several receptors by screening therapeutically relevant cell types. The ability to extract this kind of complex and physiologically relevant information about receptor ligand-induced signaling events in a native setting can also provide valuable insight into the mechanism of action of lead compounds.

For More Information

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Application Bulletin

Application Bulletin 3: Deconvolution of signal transduction pathways *

Brochure

CellKey System Brochure *

Poster

A Label-free Cell-based Assay Technology for Functional Comparison of Endogenous and Transfected Receptors *

Identification of the G-protein Coupling Mechanism of GPCRs Using a Label-free Live-Cell Assay *

Analysis of Endogenous Growth Factor Receptor Activity in Mammalian Cancer Cell Lines using a Label-Free Live-Cell Based Assay

Cataloging Endogenous Cell Surface Receptors and Analyzing Their Functional Activity using Label-Free Cellular Dielectric Spectroscopy

Complex Signaling Pathway Analysis and Pharmacological Profiling of a Transfected GPCR using Cellular Dielectric Spectroscopy, A Novel Cellular Assay Platform *

Development of a Label-Free Cellular Assay for an Endogenously Expressed GPCR Using Cellular Dielectric Spectroscopy *

Cellular Dielectric Spectroscopy: A Label-Free Technology for the Functional Evaluation of Receptor-Mediated Signaling

Other Applications

Receptor Panning

Hit Identification and Pharmalogical Profiling

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