Typical projects are aimed at assessing and/or comparing the global signaling profile of one or more target GPCRs, including receptor variants, subtypes, isoforms and orthologues.
A restricted number of ligands (usually ≤ 5) are tested using a panel of 12 biosensors for the signaling events directly associated with GPCR activity (i.e., heterotrimeric G protein biosensors for the activation of Gαs, Gαq, Gα11, Gα14, Gα15, Gαi2, GαoB, Gαz, Gα12 or Gα13; sensors for the engagement of β-arrestin 1 or β-arrestin 2).
This panel of biosensors can be complemented with those measuring more receptor-distal signaling events (i.e., generation of second messengers including cAMP, DAG, PIP3; PKC and RhoA activation; Gßɣ activity). The latter distal biosensors can also serve to confirm data previously generated by clients using other technologies.
Shown above are the distinct signaling profiles of WT and a natural C-terminal truncation mutant (Mut) of an undisclosed GPCR in response to its endogenous ligand.