Fig. (3). Signaling diversity of GPCRs: strength of signal versus conformational substates.

(A), In a two-state view of GPCR activity, where the receptor displays only a single active state, the decision of which G protein to couple to or whether to choose a G protein-independent pathway via arrestin binding must be determined by the number of receptor molecules that achieve the active state (i.e., strength of signal). (B), In a conformational substate view, since a single receptor can adopt several different active conformational substates (depicted by different colored receptors), the decision of which G protein to couple to or whether to choose a G protein-independent pathway via arrestin binding can be determined by which conformational substate is attained.