Cloning, sequencing, expression and function of a cDNA encoding a receptor for the opioid growth factor, [Met(5)]enkephalin.
The native opioid growth factor (OGF), [Met(5)]enkephalin, is a tonic inhibitory peptide that modulates cell proliferation and tissue organization during development, cancer, cellular renewal, wound healing and angiogenesis. OGF action is mediated by a receptor mechanism. We have cloned and sequenced a 2.1-kilobase (kb) cDNA for a receptor to OGF (OGFr). The open reading frame was found to encode a protein of 580 amino acids, and eight imperfect repeats of nine amino acids each were a prominent feature. The protein encoded by this cDNA exhibited the pharmacological, temporal and spatial characteristics of the OGFr. Functional studies using antisense technology demonstrated an enhancement in cell growth. The molecular organization of the OGFr has no homology to classical opioid receptors. These results provide molecular validity for the interaction of OGF and OGFr in the regulation of growth processes.
Zagon
I S
IS
Department of Neuroscience, The Pennsylvania State University, College of Medicine, 500 University Drive, Hershey, PA, USA. isz1@pus.edu
Verderame
M F
MF
Allen
S S
SS
McLaughlin
P J
PJ
D000375:Aging; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D002531:Cerebellum / Q000254:growth & development / Q000378:metabolism; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004744:Enkephalin, Methionine / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D008969:Molecular Sequence Data; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D051381:Rats; D011957:Receptors, Opioid / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000737:chemistry; D013873:Thionucleotides
D018076:DNA, Complementary; D020319:Oligodeoxyribonucleotides, Antisense; D011957:Receptors, Opioid; D011993:Recombinant Fusion Proteins; D013873:Thionucleotides; C033593:methionine-enkephalin receptor; D004744:Enkephalin, Methionine