Murine RAR beta 4 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 (RAR alpha, 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 (beta 1, beta 2, beta 3, and beta 4), which differ only in their N-terminal sequence (A domain) have been describ ed. These RAR beta isoforms display a specific pattern of expression in dev eloping and adult animals and are highly evolutionarily conserved suggestin g that they mediate distinct cellular effects of vitamin A. Experiments wer e performed to examine directly the RA-binding activity, transactivation ac tivity, and anti-AP1 activity of each of these four RAR beta isoforms. The results demonstrate that RAR beta 1, beta 2, and beta 3 bind RA with a simi lar K-d value, have a similar EC50 value in RA-dependent transactivation as says and inhibit AP1 activity to a similar level. By contrast, RAR beta 4 h as an Elevated K-d for RA, an increased EC50 value in RA-dependent transact ivation assays and does not display the ability to inhibit AP1 activity. Th is provides additional evidence that at least one RAR isoform, RAR beta 4, may mediate distinct activities within a cell. Furthermore, these data sugg est that the presence of an A domain in RAR beta is important for modulatin g these activities of RARs. J. Cell. Biochem. 77:604-614, 2000. (C) 2000 Wi ley-Liss, Inc.