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Identification of a Rat c-erbA-Related Protein Which Binds Deoxyribonucleic Acid but does not Bind Thyroid Hormone

Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Howard Hughes Medical Institute and Harvard Medical School Boston, Massachusetts 02115

Address requests for reprints to: Dr. Mitchell A. Lazar, Thorn Building, Room 913, Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts 02115.

Abstract

c-erbA cDNAs encoding thyroid hormone-binding receptor proteins have been previously isolated from several species and tissues. We have isolated a novel rat c-erbA cDNA, r-erbA-2, identical to the rat brain c-erbA cDNA (which we refer to as r-erbA-1) except at the 3'-end of the cDNA, which encodes an altered carboxy-terminal region of the predicted amino acid sequence. The r-erbA-2 cDNA is most closely related to the human testicular c-erbA cDNA. The apparent molecular weight of the in vitro protein product of this cDNA is 55 K, close to that predicted from the nucleotide sequence. The r-erbA-2 protein binds a DNA fragment containing a putative T₃-responsive sequence from the rat GH gene. However, the r-erbA-2 protein product does not bind T₃. RNA isolated from rat GH₃ cells and various rat tissues contains at least three mRNAs hybridizing to c-erbA probes. A predominant 2.6 kilobase mRNA hybridizes specifically to r-erbA-2, while a 5.0 kb mRNA hybridizes to r-erbA-1-specific cDNA probes. The r-erbA-1-related 5.0 kb mRNA is down-regulated by T₃ treatment in GH₃ cells as has previously been described for the 2.6 kb mRNA. The r-erbA-2 mRNA is most abundant in brain, whereas the r-erbA-1 mRNA is found in highest concentration in brown fat and skeletal muscle. r-erbA-1 mRNA, unlike r-erbA-2 mRNA, is undetectable in testis. Southern analyses suggest that the r-erbA-1 and r-erbA-2 mRNAs are derived from a single gene transcript.

Received for publication April 14, 1988. Accepted for publication June 15, 1988.

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