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(Received for publication, August 3,
1995; and in revised form, August 23, 1995) From the
Three types of iodothyronine deiodinase have been identified in
vertebrate tissues. cDNAs for the types I and III have been cloned and
shown to contain an in-frame TGA that codes for selenocysteine at the
active site of the enzyme. We now report the cloning of a cDNA for a
type II deiodinase using a reverse transcription/polymerase chain
reaction strategy and RNA obtained from Rana catesbeiana tissues. This cDNA (RC5`DII) manifests limited but significant
homology with other deiodinase cDNAs and contains a conserved in-frame
TGA codon. Injection of capped in vitro synthesized
transcripts of the cDNA into Xenopuslaevis oocytes
results in the induction of deiodinase activity with characteristics
typical of a type II deiodinase. The levels of RC5`DII transcripts in R. catesbeiana tadpole tail and liver mRNA at stages XII and
XXIII correspond well with that of type II deiodinase activity but not
that of the type III activity in these tissues. These findings indicate
that the amphibian type II 5`-deiodinase is a structurally unique
member of the family of selenocysteine-containing deiodinases.
Intracellular concentrations of the thyroid hormones, T The primary function of the
types I and II deiodinases is to convert T cDNAs for the type I enzyme of rat(6) , dog(7) , and
human (8) have been cloned. These cDNAs contain an in-frame TGA
coding for selenocysteine, which is necessary for maximal enzyme
activity(6) . Three cDNAs for the type III enzyme have also
been cloned; we have shown that XL-15, a cDNA isolated by Wang and
Brown (9) from a Xenopuslaevis tadpole tail
cDNA library, encodes a 5DIII (10) and, using XL-15 as a probe,
we have isolated 5DIII cDNAs for Ranacatesbeiana(11) and rat (12) . These cDNAs exhibit
significant sequence homology to the mammalian 5DI cDNAs including the
in-frame TGA codon, which codes for selenocysteine. Isolation of a
cDNA for a 5DII has yet to be reported. To this end we predicted that
this enzyme would share significant sequence homology with other
deiodinases. Close examination of the sequences of the known 5DI and
5DIII cDNAs revealed that, although the overall similarity between the
two types is relatively low, there are three limited regions that are
highly conserved. One is near the TGA codon that codes for
selenocysteine, and the other two are approximately 60 and 230 bp 3` of
this codon. We hypothesized that these regions would also be conserved
in the 5DII gene. This hypothesis proved to be correct. In the
present report we describe the cloning of a cDNA for the 5DII of R.
catesbeiana using a reverse transcription/polymerase chain
reaction (RT/PCR) strategy, oligonucleotide primers based on the
sequences of these conserved regions, and RNA from R. catesbeiana tissues that contain relatively high levels of type II 5`D
activity. Once a portion of the putative coding region of the 5DII cDNA
was obtained, gene-specific primers were used to synthesize the 3`- and
5`-ends of the cDNA using rapid amplification of cDNA ends (RACE)
procedures(13) . The resulting cDNA (RC5`DII) contains the
conserved TGA codon and codes for a protein with characteristics
typical of a 5DII.
Figure 1:
Schematic representation of the
RT/PCR-based technique used to synthesize and clone RC5`DII. A, a ``generic'' deiodinase cDNA coding region
showing the approximate locations, relative to each other, of all the
oligonucleotide primers employed. The sequences of primers A-D
are based on the ``conserved'' regions of the three 5DI and
three 5DIII deiodinase cDNAs; the sequences of primers 1-6 are
specific to RC5`DII. UAP* is a modified version of the universal
amplification primers in the RACE kits (Life Technologies, Inc.) (see
``Materials and Methods'' for details). Sense primers are
placed above, and antisense primers below, the line. B,
PCR-based approach used to synthesize the full-length RC5`DII cDNA (see
``Materials and Methods'' for
details).
The nucleotide and deduced amino acid sequences of RC5`DII
are shown in Fig. 2A. RC5`DII is a 1459-bp cDNA with an
open reading frame extending from bp 11 to 802 and an in-frame TGA
codon at bp 380-382 that, by analogy with the cDNAs for the 5DI
and 5DIII, is likely to code for selenocysteine. A schematic comparison
of the RC5`DII protein with those of R. catesbeiana type III
and the rat type I is shown in Fig. 2B. The areas of
homology are indicated, and it is also noted that the proteins exhibit
a hydrophobic region at the amino-terminal end and two histidine
residues 3` to the TGA. In the rat 5DI, these histidines have been
shown to be critical for 5`D activity (20) .
Figure 2:
A,
nucleotide and deduced amino acid sequences of RC5`DII. SC,
selenocysteine. The sequence for RC5`DII has been deposited in GenBank
under accession number L42815. B, comparison of the structural
features of three types of deiodinase (the types II and III of R.
catesbeiana and the type I of rat) as predicted by the cDNA
sequences of RC5`DII, RC5D, and G21. Regions of homology and other
shared features are noted.
5`D activity
was induced in X. laevis oocytes after injection of capped RNA
transcripts obtained by in vitro transcription of RC5`DII (Fig. 3A). No 5D activity was detected (data not
shown). The 5`D activity was not inhibited by PTU (0.1 mM),
but the percent deiodination of the [
Figure 3:
A, induction of 5`D activity in X.
laevis oocytes following injection of capped RNA transcripts (50
ng/oocyte) synthesized in vitro from the RC5`DII and the 5`DI
(G21) cDNAs. Control oocytes received no injection. Reaction mixtures
contained 45, 49.5, and 54 µg of membrane protein from control,
RC5`DII, and G21 mRNA-injected oocytes, respectively. B,
sensitivity to aurothioglucose of the 5`D activity induced in X.
laevis oocytes by RC5`DII and G21 transcripts. Values are
corrected for the 5`D activity (
In view of the indirect evidence suggesting that
the mammalian 5DII is not a selenoprotein(3) , including the
fact that it catalyzes 5`D activity that is relatively insensitive to
PTU and AThG, the possibility that the protein coded by RC5`DII is not
a selenoprotein or that selenocysteine is not involved in the activity
of the enzyme was investigated. It was found that 5`D activity in
oocytes injected with capped transcripts derived from mutant RC5`DII
cDNAs, where the TGA codon had been changed to TAA (stop) or TGT
(cysteine), was essentially the same as levels obtained in uninjected
oocytes. Furthermore, no induction of activity was observed after
injection of transcripts derived from RC5`DII truncated at bp 906,
suggesting that the deleted 3`-untranslated region contains a
selenocysteine insertion sequence. These findings provide strong
evidence that RC5`DII codes for a protein with selenocysteine at its
catalytic site. Previous studies by Berry and Larsen (3) had
led to the suggestion that sensitivity of a deiodinase to PTU and AThG
could serve as a marker for the presence of selenocysteine at the
enzyme's active site. That this is not a valid criterion is
demonstrated by the presence of the TGA coding for selenocysteine in
the RC5`DII cDNA described herein and in three recently isolated type
III deiodinase cDNAs, all of which encode enzymes resistant to PTU and
AThG(10, 11, 12) . Thus other structural
properties of these enzymes or differences in kinetic mechanisms may
dictate PTU and AThG sensitivity. The ontogenic profiles of 5`D and
5D activities in R. catesbeiana tadpole tail and liver are
very different; 5`D activity is minimal in tadpole tail until the onset
of metamorphic climax when it increases markedly reaching a maximum by
stage XXIII, while liver is devoid of 5`D activity at all stages of
development (21) . In contrast, 5D activity is present in both
tail and liver during premetamorphosis, and in liver it is greatly
reduced when the tadpoles reach metamorphic climax(22) . To
obtain additional evidence concerning the identity of RC5`DII, the size
and relative abundance of RC5`DII-related transcripts in tail and liver
poly(A)
Figure 4:
Northern analysis of RC5`DII-related
transcripts in poly(A)
Additional evidence that RC5`DII is
an amphibian type II deiodinase is provided by our recent
identification of rat and human homologues of this cDNA. Both are
highly homologous to RC5`DII within the coding region (rat, 71%; human,
73%). Furthermore, the tissue distribution of their related mRNA
transcripts, as determined by Northern analysis, is characteristic of
the mammalian type II enzyme. ( We thus conclude that
RC5`DII is the cDNA for the 5DII in R. catesbeiana. The
characteristics of the deiodinase for which it codes are comparable
with those of the 5`D activity in R. catesbeiana tadpole
tissues (5) and in mammalian brain, pituitary, and brown
fat(1) . The fact that type I 5`D activity has not been
detected in tissues of this amphibian species (5, 21) makes it highly unlikely that RC5`DII codes
for a form of the type I deiodinase. In addition, the data strongly
suggest that the type II deiodinase coded by RC5`DII is a
selenoprotein. We have compared the protein sequences deduced from the
seven cloned deiodinase cDNAs, and it is evident that the RC5`DII
protein has limited but significant homology with both the type I and
the type III enzymes. Thus the amphibian type II deiodinase represents
a structurally unique member of this family of
selenocysteine-containing enzymes.
The nucleotide sequence(s) reported in this paper has been submitted
to the GenBank(TM)/EMBL Data Bank with accession number(s)
L42815[GenBank].
Volume 270,
Number 45,
Issue of November 10, 1995 pp. 26786-26789
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.
(
)and T
, are profoundly influenced by the
activity of three iodothyronine deiodinases, classified as types I, II,
and III (1) . In mammals, the type I enzyme (5DI) catalyzes
5`-deiodination (5`D), the removal of iodine from the 5` (or 3`)
positions of T and its derivatives. The enzyme can also
catalyze 5-deiodination (5D), the removal of an iodine located at
either the 5 (or 3) positions of iodothyronines, but does so
efficiently only with sulfated iodothyronine substrates(2) .
The type II enzyme (5DII) also catalyzes 5`D, but it is readily
distinguished from the 5DI by its kinetics, substrate specificity,
sensitivity to propylthiouracil (PTU) and aurothioglucose
(AThG)(1, 3) , and response to thyroid
status(1) . The type III enzyme (5DIII) catalyzes primarily 5D
activity(1) , a process that results in derivatives with little
or no thyromimetic activity(1) . to its
metabolically more active derivative, T. However, the
tissue distribution and physiological roles of the two enzymes are very
different. The principal role of the 5DI in mammals is to provide a
source of plasma T by deiodination of T in
peripheral tissues such as liver and kidney. In contrast, the 5DII is
responsible for the majority of the intracellular T in
tissues such as the pituitary, brain, and brown fat by mediating local
deiodination of T and is considered to be of major
importance in regulating thyroid hormone action in these
tissues(1, 3) . The 5DII also plays a major role
during development. 5DII is the principal 5`-deiodinase expressed in
the mammalian fetus, and it is notable that 5DII activity in brain
peaks in the neonatal period, the time that is critical for thyroid
hormone-dependent development in this tissue(4) . Moreover,
5DII is the only 5`-deiodinase present in the developing frog in which
the orderly progression of developmental processes is dependent on the
ability to attain appropriate intracellular levels of
T(5) . Thus, the 5DII appears to play an essential
role in intracellular T3 production in those circumstances where
thyroid hormone-dependent processes take on critical significance.
Animals
R. catesbeiana tadpoles, stages
XX-XXIV (Taylor and Kollros(14) ), were obtained from
Charles D. Sullivan, Inc., Nashville, TN. Maintenance of tadpoles and
preparation of total and poly(A) RNA from their
tissues were carried out as described previously(15) .
Synthesis of a Partial cDNA for the 5DII from R.
catesbeiana Tissues
The sequences of the primers used in the
synthesis of the cDNA for the 5DII of R. catesbeiana are shown
in Table 1. Lettered primers (A, B, C, and D) are based on the
conserved sequences of the 5DI and 5DIII cDNAs; numbered primers (1, 2, 3, 4, 5, 6) are
specific to the RC5`DII cDNA. Their locations relative to each other in
RC5`DII are shown in Fig. 1A. A schematic
representation of the RT/PCR-based cloning strategy is shown in Fig. 1B. Total RNA obtained from the hindlimb of
tadpoles was reverse transcribed using primer C, and the resulting cDNA
was amplified by PCR using primers A and C. The following cycling
conditions were used in this and all subsequent PCR reactions: 94
°C for 45 s; 52 °C for 45 s; 72 °C for 60 s, with a 2-s
extension at 72 °C for each of 30 cycles. This was followed by a
10-min extension at 72 °C. The 110-bp product obtained was
reamplified with primers A and B to yield a 98-bp product whose
sequence, excluding the primers, exhibited 46% identity with the
corresponding sequence in the R. catesbeiana 5DIII cDNA
(RC5D). Then skin RNA from stage XXIII tadpoles was reverse transcribed
using the oligo(dT) adapter primer from the 3`-RACE kit (Life
Technologies, Inc.), and the resulting cDNA was amplified using primers
1 and D to yield a 238-bp product, whose sequence was 48% identical to
that of RC5D. This sequence information revealed that the 32
nucleotides in the ``conserved'' region used to design
primers B and C are 84% identical to those in RC5D.
Synthesis of the 3`- and 5`-Ends of RC5`DII Using the
RACE Procedure
The 3`- and 5`-RACE procedures were carried out
as recommended by the manufacturer (Life Technologies, Inc.) with one
exception. Since in our experience the universal amplification primer
(UAP), which is used in both procedures, routinely makes multiple
products, a modified UAP (UAP*) was designed. The 12 nucleotides at the
5`-end, which are only necessary if the kit's cloning procedure
is employed, were eliminated and, with the aid of a computer program
(OLIGO 4.0, National Biosciences, Inc., Plymouth, MN), the
remaining UAP sequence, 5`-GGCCACGCGTCGACTAGTAC-3`, was modified to
5`-GTCCACGCATCGACTAGTA-3`. The 3`-end of RC5`DII was synthesized using
the cDNA obtained from skin RNA (see above) as template. Two rounds of
PCR, the first with primers 2 and UAP* and the second with nested
primer 3 and UAP*, yielded a product of about 1000 bp. The overlapping
5`-end was made from skin RNA, which was reverse transcribed with
primer 6, and the resulting cDNA was subjected to two rounds of PCR,
the first with primers UAP* and 5 and the second with UAP and 4, to
yield a 600-bp product. The two halves of RC5`DII, which overlapped by
92 bp, were joined to yield the full-length RC5`DII cDNA by overlap
extension PCR(16) . This reaction mixture contained equimolar
amounts of the two products and the UAP* primer. The approximately
1500-bp product of this PCR was cloned into pBluescript using the
PCR-Script kit (Stratagene, La Jolla, CA) and sequenced. To check for
potential PCR errors, the entire cDNA was synthesized three times in
separate RT/PCR reactions. Three errors were found, none of which was
in the coding region.
Expression of RC5`DII in X. laevis Oocytes
In
vitro synthesized, capped RNA transcripts of the putative 5DII cDNA
were prepared using the MEGAscript kit (Ambion, Austin, TX) and
injected into stage 5-6 X. laevis oocytes (50 ng of
RNA/oocyte). Groups of oocytes were also injected with capped
transcripts synthesized from a rat 5DI cDNA (G21, provided by Drs.
Marla Berry and Reed Larsen, Boston, MA). The oocytes were incubated
for 4 days in L-15 medium and then harvested, and membrane fractions
were prepared as described by Sharifi and St. Germain(17) , and
5`D and 5D activities were measured according to published
methods(17, 18) . For the 5`D assay, the substrate was
1 nM [I]rT
with
0-120 nM nonradioactive rT, and the cofactor
was 20 mM dithiothreitol; for the 5D assay, 1 nM
[I]T
was used as substrate and 50
mM dithiothreitol as cofactor.
[I]Iodothyronines (Dupont de Nemours & Co.,
Boston, MA) were purified by chromatography using Sephadex LH-20
(Sigma) before use. In some experiments the effect of PTU
(0.001-0.1 mM) and AThG (0.1-100 µM)
on 5`D activity was examined.
Functional Analysis of RC5`DII by Deletion and
Mutation
RC5`DII was truncated in the 3`-untranslated region at
position 906 using DraI. Mutants of RC5`DII were made in which
the in-frame TGA codon (bp 380-382) was changed either to a TAA
(stop) or to a TGT (cysteine) codon. The sequences of these mutants
were verified. The ability of capped in vitro synthesized RNA
transcripts of these cDNAs to induce 5`D activity following injection
into X. laevis oocytes was then determined.Analysis of RNA
Samples of
poly(A) RNA from tissues of premetamorphic tadpoles
(stages X-XII) and tadpoles undergoing metamorphic climax (stages
XXIII-XXIV) were examined for the presence of RC5`DII-specific
transcripts by Northern and slot blot analyses using methods previously
described(19) . Hybridizations and washings were carried out,
respectively, at 42 and 50 °C. Signals were visualized by
autoradiography and quantitated with the 628E PhosphorImager (Molecular
Dynamics). Data are reported as arbitrary densitometric units.
I]rT
was greatly reduced in the presence of 3 nM non-radioactive rT, indicating that the enzyme
manifests a low K
for this substrate. We have
shown previously that the 5`D activity in tadpole tissues exhibits a
low K and is resistant to inhibition by
PTU(5, 21) , characteristics that are typical of the
type II 5`D activity described in mammals(1) . In contrast,
capped transcripts of the 5DI cDNA, G21, induced activity that was
highly sensitive to PTU and appeared to have a relatively high K. In addition, the 5`D activity induced by the
RC5`DII transcripts was relatively insensitive to inhibition by AThG (Fig. 3B). The 5`D activity induced in oocytes by
RC5`DII transcripts was considerably lower than that induced by
transcripts of the G21 cDNA. The reason for this difference is not
known. However, 5`D activity is only minimally induced in X. laevis oocytes by rat brown adipose tissue mRNA, a tissue containing
considerable type II 5`D activity, (
)and it is possible that
other factors important for type II 5`D activity are not optimal in
this oocyte system.
2%) observed in uninjected
oocytes. Reaction mixtures contained 48 and 21 µg of membrane
protein from the RC5`DII and G21 mRNA-injected oocytes,
respectively.
RNA obtained from premetamorphic (stage
X-XII) and metamorphosing (stage XXIII) tadpoles were determined
by Northern analysis (Fig. 4). No RC5`DII transcripts were
detected in liver mRNA at either stage of development. This finding is
consistent with the absence of 5`D activity in this tissue at all
stages of the life cycle(5, 21) . However, a major RNA
species of approximately 1.5 kb was detected in tail RNA; two minor
species were just discernible at approximately 1.8 and 2.2 kb. The
2.2-kb species may represent cross-hybridization with RC5D transcripts
since comparable blots probed with RC5D exhibit a signal at 2.2 kb
(data not shown). In other blots a minor species was also detected at
approximately 7.4 kb. The level of the 1.5-kb species was much higher
in RNA from metamorphosing tail than in that from premetamorphic tail.
Thus the profile of RC5`DII transcripts in liver and tail corresponds
closely to that of 5`D but not 5D activity in these tissues. The
increase in RC5`DII mRNA species in tail during metamorphic climax was
quantified using slot blot analysis. Densitometric analysis indicated
that the hybridization signals in tadpole tail at stages X-XII
and stages XXIII-XXIV were, respectively, 280 ± 50 (S.E.)
and 5151 ± 345 units (p < 0.001). As with the
Northern blot, no signal was observed in liver RNA. Reprobing of the
blot with RC5D revealed that levels of RC5D transcripts, which were
clearly evident in both liver and tail at both stages of development,
were not increased during metamorphic climax (data not shown). Thus,
the observed increase in the level of RC5`DII-related transcripts on
the blot cannot be attributed even in part to cross-hybridization of
RC5`DII with RC5D transcripts.
RNA from tadpole tail and
liver. P, poly(A)
RNA from premetamorphic
(stage XII) tadpoles; M, poly(A)
RNA from
metamorphosing (stage XXIII) tadpoles.
)
), thyroxine; T,
3,5,3`-triiodothyronine; rT, 3,3`,5`-triiodothyronine; 5DI,
type I deiodinase; 5DII, type II deiodinase; 5DIII, type III
deiodinase; 5`D, 5`-deiodination; 5D, 5-deiodination; RC5D, cDNA for
the R. catesbeiana type III deiodinase; bp, base pair(s); kb,
kilobase(s); PTU, 6n-propyl 2-thiouracil; AThG,
aurothioglucose; RT/PCR, reverse transcription/polymerase chain
reaction; RACE, rapid amplification of cDNA ends; UAP, universal
amplification primer.))
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.
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 M. Murakami, O. Araki, T. Morimura, Y. Hosoi, H. Mizuma, M. Yamada, H. Kurihara, S. Ishiuchi, M. Tamura, T. Sasaki, et al. Expression of Type II Iodothyronine Deiodinase in Brain Tumors J. Clin. Endocrinol. Metab., November 1, 2000; 85(11): 4403 - 4406. [Abstract] [Full Text]
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J. M. Bates, Vickie. L. Spate, J. S. Morris, D. L. St. Germain, and V. A. Galton Effects of Selenium Deficiency on Tissue Selenium Content, Deiodinase Activity, and Thyroid Hormone Economy in the Rat during Development Endocrinology, July 1, 2000; 141(7): 2490 - 2500. [Abstract] [Full Text] [PDF]
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Y. Hosoi, M. Murakami, H. Mizuma, T. Ogiwara, M. Imamura, and M. Mori Expression and Regulation of Type II Iodothyronine Deiodinase in Cultured Human Skeletal Muscle Cells J. Clin. Endocrinol. Metab., September 1, 1999; 84(9): 3293 - 3300. [Abstract] [Full Text]
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J. P. Sanders, S. Van der Geyten, E. Kaptein, V. M. Darras, E. R. Kühn, J. L. Leonard, and T. J. Visser Cloning and Characterization of Type III Iodothyronine Deiodinase from the Fish Oreochromis niloticus Endocrinology, August 1, 1999; 140(8): 3666 - 3673. [Abstract] [Full Text]
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B. Gereben, T. Bartha, H. M. Tu, J. W. Harney, P. Rudas, and P. R. Larsen Cloning and Expression of the Chicken Type 2 Iodothyronine 5'-Deiodinase J. Biol. Chem., May 14, 1999; 274(20): 13768 - 13776. [Abstract] [Full Text] [PDF]
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J. L. Leonard, D. M. Leonard, M. Safran, R. Wu, M. L. Zapp, and A. P. Farwell The Mammalian Homolog of the Frog Type II Selenodeiodinase Does Not Encode a Functional Enzyme in the Rat Endocrinology, May 1, 1999; 140(5): 2206 - 2215. [Abstract] [Full Text]
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Y. Kamiya, M. Murakami, O. Araki, Y. Hosoi, T. Ogiwara, H. Mizuma, and M. Mori Pretranslational Regulation of Rhythmic Type II Iodothyronine Deiodinase Expression by {beta}-Adrenergic Mechanism in the Rat Pineal Gland Endocrinology, March 1, 1999; 140(3): 1272 - 1278. [Abstract] [Full Text]
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Y. Saito, T. Hayashi, A. Tanaka, Y. Watanabe, M. Suzuki, E. Saito, and K. Takahashi Selenoprotein P in Human Plasma as an Extracellular Phospholipid Hydroperoxide Glutathione Peroxidase. ISOLATION AND ENZYMATIC CHARACTERIZATION OF HUMAN SELENOPROTEIN P J. Biol. Chem., January 29, 1999; 274(5): 2866 - 2871. [Abstract] [Full Text] [PDF]
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A. Hernández, G. J. Lyon, M. J. Schneider, and D. L. St. Germain Isolation and Characterization of the Mouse Gene for the Type 3 Iodothyronine Deiodinase Endocrinology, January 1, 1999; 140(1): 124 - 130. [Abstract] [Full Text]
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C. Buettner, J. W. Harney, and P. R. Larsen The 3'-Untranslated Region of Human Type 2 Iodothyronine Deiodinase mRNA Contains a Functional Selenocysteine Insertion Sequence Element J. Biol. Chem., December 11, 1998; 273(50): 33374 - 33378. [Abstract] [Full Text] [PDF]
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W. Croteau, J. E. Bodwell, J. M. Richardson, and D. L. St. Germain Conserved Cysteines in the Type 1 Deiodinase Selenoprotein Are Not Essential for Catalytic Activity J. Biol. Chem., September 25, 1998; 273(39): 25230 - 25236. [Abstract] [Full Text] [PDF]
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J. P. Schroder-van der Elst, D. van der Heide, G. Morreale de Escobar, and M. J. Obregon Iodothyronine Deiodinase Activities in Fetal Rat Tissues at Several Levels of Iodine Deficiency: A Role for the Skin in 3,5,3'-Triiodothyronine Economy? Endocrinology, May 1, 1998; 139(5): 2229 - 2234. [Abstract] [Full Text] [PDF]
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A. Hernandez, D. L. St. Germain, and M. J. Obregon Transcriptional Activation of Type III Inner Ring Deiodinase by Growth Factors in Cultured Rat Brown Adipocytes Endocrinology, February 1, 1998; 139(2): 634 - 639. [Abstract] [Full Text] [PDF]
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S. Van der Geyten, J. P. Sanders, E. Kaptein, V. M. Darras, E. R. Kuhn, J. L. Leonard, and T. J. Visser Expression of Chicken Hepatic Type I and Type III Iodothyronine Deiodinases during Embryonic Development Endocrinology, December 1, 1997; 138(12): 5144 - 5152. [Abstract] [Full Text] [PDF]
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J. P. Sanders, S. Van der Geyten, E. Kaptein, V. M. Darras, E. R. Kuhn, J. L. Leonard, and T. J. Visser Characterization of a Propylthiouracil-Insensitive Type I Iodothyronine Deiodinase Endocrinology, December 1, 1997; 138(12): 5153 - 5160. [Abstract] [Full Text] [PDF]
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L. A. Burmeister, J. Pachucki, and D. L. St. Germain Thyroid Hormones Inhibit Type 2 Iodothyronine Deiodinase in the Rat Cerebral Cortex by Both Pre- and Posttranslational Mechanisms Endocrinology, December 1, 1997; 138(12): 5231 - 5237. [Abstract] [Full Text] [PDF]
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B. C. Sun, J. W. Harney, M. J. Berry, and P. R. Larsen The Role of the Active Site Cysteine in Catalysis by Type 1 Iodothyronine Deiodinase Endocrinology, December 1, 1997; 138(12): 5452 - 5458. [Abstract] [Full Text] [PDF]
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L. Navarro, A. Landa, C. Valverde-R, and C. Aceves Mammary Gland Type I Iodothyronine Deiodinase Is Encoded by a Short Messenger Ribonucleic Acid Endocrinology, October 1, 1997; 138(10): 4248 - 4254. [Abstract] [Full Text] [PDF]
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S. Pallud, A.-M. Lennon, M. Ramauge, J.-M. Gavaret, W. Croteau, M. Pierre, F. Courtin, and D. L. St. Germain Expression of the Type II Iodothyronine Deiodinase in Cultured Rat Astrocytes Is Selenium-dependent J. Biol. Chem., July 18, 1997; 272(29): 18104 - 18110. [Abstract] [Full Text] [PDF]
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K. B. Becker, K. C. Stephens, J. C. Davey, M. J. Schneider, and V. A. Galton The Type 2 and Type 3 Iodothyronine Deiodinases Play Important Roles in Coordinating Development in Rana catesbeiana Tadpoles Endocrinology, July 1, 1997; 138(7): 2989 - 2997. [Abstract] [Full Text] [PDF]
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H. F. Escobar-Morreale, M. J. Obregon, A. Hernandez, F. Escobar del Rey, and G. Morreale de Escobar Regulation of Iodothyronine Deiodinase Activity as Studied in Thyroidectomized Rats Infused with Thyroxine or Triiodothyronine Endocrinology, June 1, 1997; 138(6): 2559 - 2568. [Abstract] [Full Text] [PDF]
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K. A. Mol, S. van der Geyten, V. M. Darras, T. J. Visser, and E. R. Kuhn Characterization of Iodothyronine Outer Ring and Inner Ring Deiodinase Activities in the Blue Tilapia, Oreochromis Aureus Endocrinology, May 1, 1997; 138(5): 1787 - 1793. [Abstract] [Full Text] [PDF]
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J.-Y. Yeh, Q.-P. Gu, M. A. Beilstein, N. E. Forsberg, and P. D. Whanger Selenium Influences Tissue Levels of Selenoprotein W in Sheep J. Nutr., March 1, 1997; 127(3): 394 - 402. [Abstract] [Full Text]
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C. Valverde-R, W. Croteau, G. J. LaFleur Jr., A. Orozco, and D. L. St. Germain Cloning and Expression of a 5'-Iodothyronine Deiodinase from the Liver of Fundulus heteroclitus Endocrinology, February 1, 1997; 138(2): 642 - 648. [Abstract] [Full Text] [PDF]
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 D. Robinson and L Cooley Examination of the function of two kelch proteins generated by stop codon suppression Development, January 4, 1997; 124(7): 1405 - 1417. [Abstract] [PDF]
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N. Toyoda, E. Kaptein, M. J. Berry, J. W. Harney, P. R. Larsen, and T. J. Visser Structure-Activity Relationships for Thyroid Hormone Deiodination by Mammalian Type I Iodothyronine Deiodinases Endocrinology, January 1, 1997; 138(1): 213 - 219. [Abstract] [Full Text] [PDF]
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A. Orozco, J. E. Silva, and C. Valverde-R Rainbow Trout Liver Expresses Two Iodothyronine Phenolic Ring Deiodinase Pathways with the Characteristics of Mammalian Types I and II 5'-Deiodinases Endocrinology, January 1, 1997; 138(1): 254 - 258. [Abstract] [Full Text] [PDF]
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M. Safran, A. P. Farwell, and J. L. Leonard Catalytic Activity of Type II Iodothyronine 5'-Deiodinase Polypeptide Is Dependent upon a Cyclic AMP Activation Factor J. Biol. Chem., July 5, 1996; 271(27): 16363 - 16368. [Abstract] [Full Text] [PDF]
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D. M. Leonard, S. J. Stachelek, M. Safran, A. P. Farwell, T. F. Kowalik, and J. L. Leonard Cloning, Expression, and Functional Characterization of the Substrate Binding Subunit of Rat Type II Iodothyronine 5'-Deiodinase J. Biol. Chem., August 11, 2000; 275(33): 25194 - 25201. [Abstract] [Full Text] [PDF]
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H. Huang, L. Cai, B. F. Remo, and D. D. Brown Timing of metamorphosis and the onset of the negative feedback loop between the thyroid gland and the pituitary is controlled by type II iodothyronine deiodinase in Xenopus laevis PNAS, June 19, 2001; 98(13): 7348 - 7353. [Abstract] [Full Text] [PDF]
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