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

Steroid hormones induce the transcriptional activity of their cognate receptors by recruiting a variety of cofactors. One of these, steroid receptor co-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 preferentially interact with motif 4. We show that the interactions depend not only on the LXXLL motif itself but also on residues flanking the motif. (C) 2000 Elsevier Science Ltd. All rights reserved.