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PMID: 7753868 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

LEM1, an ATP-binding-cassette transporter, selectively modulates the biological potency of steroid hormones.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 92 ·No. 10 ·1995-05-09 ·Pages 4701-5

Kralli A, Bohen SP, Yamamoto KR

Abstract

The rat glucocorticoid receptor confers hormone-dependent transcriptional enhancement when expressed in yeast, thereby enabling the genetic identification of nonreceptor proteins that function in the hormone signal-transduction pathway. We isolated a yeast mutant, lem1, with increased sensitivity to dexamethasone and triamcinolone acetonide; responsiveness to a third agonist, deoxycorticosterone, is unaffected. Cloning of wild-type LEM1 revealed a putative transport protein of the ATP-binding cassette family. Dexamethasone accumulation is increased in lem1 cells, suggesting that wild-type LEM1 decreases dexamethasone potency by exporting this ligand. LEM1 appears to affect certain steroids and not others. We propose that transporters like LEM1 can selectively modulate the intracellular levels of steroid hormones. Differential activities of such transporters in mammalian cells might regulate hormone availability and thereby hormone signaling in a cell-type specific manner.

MeSH Terms
ATP-Binding Cassette Transporters/biosynthesis,metabolism Adenosine Triphosphate/metabolism Animals Carrier Proteins/metabolism Cloning, Molecular Desoxycorticosterone/pharmacology Dexamethasone/metabolism,pharmacology Estradiol/metabolism Ethyl Methanesulfonate/pharmacology Genetic Complementation Test Kinetics Mammals Mutagenesis Rats Receptors, Estrogen/metabolism Receptors, Glucocorticoid/metabolism Receptors, Steroid/drug effects,metabolism Recombinant Proteins/metabolism Saccharomyces cerevisiae/drug effects,genetics,metabolism Saccharomyces cerevisiae Proteins Triamcinolone Acetonide/pharmacology
Chemicals
ATP-Binding Cassette Transporters Carrier Proteins PDR5 protein, S cerevisiae Receptors, Estrogen Receptors, Glucocorticoid Receptors, Steroid Recombinant Proteins Saccharomyces cerevisiae Proteins Desoxycorticosterone Estradiol Dexamethasone Adenosine Triphosphate Ethyl Methanesulfonate Triamcinolone Acetonide
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Kralli A
Department of Cellular and Molecular Pharmacology, University of California, San Francisco 94143-0448, USA.
Bohen S P
Yamamoto K R
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.92.10.4701
Published
1995-05-09
Pages
4701-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC42012
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.92.10.4701 PMC Full Text View journal details
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