Murine RARbeta4 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 (RARalpha, beta, and gamma) and retinoid X receptors (RXR alpha, beta, and gamma). Each of the RARs is expressed as four to seven different isoforms. Four isoforms of RAR beta (beta1, beta2, beta3, and beta4), which differ only in their N-terminal sequence (A domain) have been described. These RARbeta 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 RARbeta isoforms. The results demonstrate that RARbeta1, beta2, and beta3 bind RA with a similar K(d) value, have a similar EC(50) value in RA-dependent transactivation assays and inhibit AP1 activity to a similar level. By contrast, RARbeta4 has an elevated K(d) for RA, an increased EC(50) 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, RARbeta4, may mediate distinct activities within a cell. Furthermore, these data suggest that the presence of an A domain in RARbeta is important for modulating these activities of RARs. Copyright 2000 Wiley-Liss, Inc.