LIGAND SPECIFICITIES OF RECOMBINANT RETINOIC ACID RECEPTORS RAR-ALPHA AND RAR-BETA

Binding of retinoic acid (RA) to specific RA receptors α and β (RARα and RARβ) was studied. Receptors were obtained in two ways: (1) full-length receptors were produced by transient expression of the respective human cDNAs in COS 1 cells; and (2) the ligand-binding domains of RARα and RARβ were produced in Escherichia coli. RA binding to the wild-type and truncated forms of the receptor was identical for both RARα and RARβ, indicating that the ligand-binding domains have retained the binding characteristics of the intact receptors. Furthermore, RA bound with the same affinity to both RARα and RARβ. Only retinoid analogues with an acidic end-group were able to actively bind to both receptors. On measuring the binding of various retinoids, we have found that the properties of the ligand-binding sites of RARα and RARβ were rather similar. Two retinoid analogues were capable of binding preferentially to either RARα or RARβ, suggesting that it may be possible to synthesize specific ligands for RARα and RARβ.