Differential interaction of steroid hormone receptors with LXXLL motifs inSRC-1a depends on residues flanking the motif

Steroid hormones induce the transcriptional activity of their cognate recep tors by recruiting a variety of cofactors. One of these, steroid receptor c o-activator-1 (SRC-1) interacts with the ligand binding domains of a number of different receptors by means of LXXLL motifs. We have investigated the relative interaction of four such motifs in SR%-1a using a yeast two-hybrid assay. We demonstrate that ER alpha, ER beta and ER beta 2 preferentially interact with motif 2 while GR, AR, PPAR alpha and PPAR gamma preferentiall y interact with motif 4. We show that the interactions depend not only on t he LXXLL motif itself but also on residues flanking the motif. (C) 2000 Els evier Science Ltd. All rights reserved.