Document Detail


Cloning and characterization of a complementary DNA for a thyroid hormone-responsive protein in mature rat cerebral tissue.
MedLine Citation:
PMID:  9359437     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A gene responsive to thyroid hormone (TH) has been identified in the adult rat brain cerebral tissue. A cDNA probe differentially expressed in euthyroid, hypothyroid and hyperthyroid rat cerebral tissue, generated by reverse transcriptase-PCR differential display of mRNA, was used to screen the rat brain cDNA library. A 3.4 kb positive clone hybridized in Northern blots with a 3.8 kb mRNA that proved to be TH responsive (THR). The remaining coding sequence and a part of the 5' untranslated region of this cDNA were obtained by 5' rapid amplification of cDNA ends. The deduced amino acid sequence revealed that THR protein (THRP), a 68 kDa moiety, has 83% sequence similarity with c-Abl interactor protein (Abi-2), which is a substrate for tyrosine kinase activity of c-Abl. The extensive similarity between the two proteins suggests a potential role for THRP as a substrate for c-Abl. Northern analysis showed that the expression of THR mRNA in hyperthyroid rats is 6-fold that in euthyroid rats. There is also a 4-6-fold increase in the concentration of THRP, as analysed by Western analysis. Owing to the extensive similarity between rat THRP and human Abi-2, a polyclonal anti- (human Abi-2) antibody was successfully used for Western analysis of proteins from the rat tissues. The observed increase in both the mRNA and the protein did not decline after beta-adrenergic system blockade with propranolol, suggesting that the action of TH on the expression of this gene is not mediated through the beta-adrenergic system. Immunohistochemical studies revealed that neuronal cells were particularly rich in THRP. Both THR mRNA and THRP are rapidly induced in vivo after intravenous administration of thyroxine. Tissue distribution studies indicated that the cerebral tissue was particularly enriched with THR mRNA and 68 kDa THRP. A cDNA clone for a THR gene could provide a useful tool to study the molecular mechanisms of TH effects on cerebral tissue in adult animals.
Authors:
G N Shah; J Li; P Schneiderjohn; A D Mooradian
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Biochemical journal     Volume:  327 ( Pt 2)     ISSN:  0264-6021     ISO Abbreviation:  Biochem. J.     Publication Date:  1997 Oct 
Date Detail:
Created Date:  1997-12-08     Completed Date:  1997-12-08     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  617-23     Citation Subset:  IM    
Affiliation:
Division of Endocrinology, St. Louis University Medical School, 1402 South Grand Blvd., St. Louis, MO 63104, USA.
Data Bank Information
Bank Name/Acc. No.:
GENBANK/U94904
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MeSH Terms
Descriptor/Qualifier:
Adaptor Proteins, Signal Transducing
Amino Acid Sequence
Analysis of Variance
Animals
Antibodies
Base Sequence
Blotting, Western
Brain / metabolism*
Cloning, Molecular
DNA, Complementary
Gene Expression Regulation / drug effects,  physiology*
Homeodomain Proteins / biosynthesis*,  chemistry
Humans
Hyperthyroidism / metabolism
Hypothyroidism / metabolism
Kinetics
Male
Molecular Sequence Data
Organ Specificity
Propranolol / pharmacology
RNA, Messenger / biosynthesis
Rats
Rats, Inbred F344
Sequence Alignment
Sequence Homology, Amino Acid
Thyroid Gland / physiology*
Chemical
Reg. No./Substance:
0/ABI2 protein, human; 0/Abi2 protein, mouse; 0/Abi2 protein, rat; 0/Adaptor Proteins, Signal Transducing; 0/Antibodies; 0/DNA, Complementary; 0/Homeodomain Proteins; 0/RNA, Messenger; 525-66-6/Propranolol
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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