Murine RARβ4 displays reduced transactivation activity, lower affinity for retinoic acid, and no anti-AP1 activity

The biological actions of retinoic acid (RA) are mediated by retinoic acid receptors (RARα, β, and γ) and retinoid X receptors (RXR α, β, and γ). Each of the RARs is expressed as four to seven different isoforms. Four isoforms of RAR β (β1, β2, β3, and β4), which differ only in their N-terminal sequence (A domain) have been described. These RARβ isoforms display a specific pattern of expression in developing and adult animals and are highly evolutionarily conserved suggesting that they mediate distinct cellular effects of vitamin A. Experiments were performed to examine directly the RA-binding activity, transactivation activity, and anti-AP1 activity of each of these four RARβ isoforms. The results demonstrate that RARβ1, β2, and β3 bind RA with a similar Kd value, have a similar EC50 value in RA-dependent transactivation assays and inhibit AP1 activity to a similar level. By contrast, RARβ4 has an elevated Kd for RA, an increased EC50 value in RA-dependent transactivation assays and does not display the ability to inhibit AP1 activity. This provides additional evidence that at least one RAR isoform, RARβ4, may mediate distinct activities within a cell. Furthermore, these data suggest that the presence of an A domain in RARβ is important for modulating these activities of RARs. J. Cell. Biochem. 77:604–614, 2000. © 2000 Wiley-Liss, Inc.