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 SRC-1a using a yeast two-hybrid assay. We demonstrate that ERalpha, ERbeta and ERbeta2 preferentially interact with motif 2 while GR, AR, PPARalpha and PPARgamma 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.
Needham
M
M
AstraZeneca Pharmaceuticals, Alderley Park, Macclesfield, Cheshire, UK.
Raines
S
S
McPheat
J
J
Stacey
C
C
Ellston
J
J
Hoare
S
S
Parker
M
M
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D001665:Binding Sites; D003907:Dexamethasone / Q000378:metabolism; D013196:Dihydrotestosterone / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism; D051548:Histone Acetyltransferases; D006801:Humans; D007930:Leucine / Q000235:genetics / Q000378:metabolism*; D008024:Ligands; D056920:Nuclear Receptor Coactivator 1; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D011944:Receptors, Androgen / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D011987:Receptors, Steroid / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity; D013816:Thermodynamics; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
D004967:Estrogens; D008024:Ligands; D010455:Peptides; D011944:Receptors, Androgen; D018160:Receptors, Cytoplasmic and Nuclear; D011960:Receptors, Estrogen; D011965:Receptors, Glucocorticoid; D011987:Receptors, Steroid; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D013196:Dihydrotestosterone; D003907:Dexamethasone; D051548:Histone Acetyltransferases; C538859:NCOA1 protein, human; D056920:Nuclear Receptor Coactivator 1; D007930:Leucine