Identification of a new member of the steroid hormone receptor superfamily that is activated by a peroxisome proliferator and fatty acids.
We have identified a novel member of the steroid hormone receptor superfamily by cDNA cloning from a human osteosarcoma SAOS-2/B10 cell library. Sequence analysis predicts a protein of 441 amino acids, which includes the conserved amino acid residues characteristic of the DNA- and ligand-binding domains of nuclear receptors. Amino acid sequence alignment and transcriptional activation experiments revealed that the new protein is closely related to the mouse peroxisome proliferator activated receptor. The overall homology is 62%, and the highest similarity is seen in the DNA- and ligand-binding domains, 86% and 71%, respectively. Northern blot analysis showed that in mature rats, the receptor is highly expressed in heart, kidney, and lung as a transcript of approximately 3500 nucleotides. In human cells, the size of the mRNA is approximately 4000 nucleotides. Transcription assays using hybrid receptors consisting of the ligand-binding domain of the new protein and the DNA-binding domain of the glucocorticoid receptor showed weak stimulation by the peroxisome proliferator activator WY14643, suggesting a relationship to that receptor. Similar stimulation was observed with arachidonic and oleic acid (100-250 microM).
Schmidt
A
A
Department of Bone Biology and Osteoporosis Research, Merck Research Laboratories, West Point, Pennsylvania 19486.
Endo
N
N
Rutledge
S J
SJ
Vogel
R
R
Shinar
D
D
Rodan
G A
GA
D000595:Amino Acid Sequence; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D001483:Base Sequence; D001665:Binding Sites; D002467:Cell Nucleus / Q000378:metabolism*; D003001:Cloning, Molecular; D003907:Dexamethasone / Q000494:pharmacology*; D015723:Gene Library; D006801:Humans; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D019301:Oleic Acid; D009829:Oleic Acids / Q000494:pharmacology*; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; D012516:Osteosarcoma; D016133:Polymerase Chain Reaction / Q000379:methods; D011743:Pyrimidines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics*; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D009829:Oleic Acids; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; D011743:Pyrimidines; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D016718:Arachidonic Acid; D019301:Oleic Acid; D003907:Dexamethasone; C006253:pirinixic acid