| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
(Received for publication, October 27,
1995; and in revised form, November 13, 1995) From the
Myotrophin is a soluble-12 kilodalton protein isolated from
hypertrophied spontaneously hypertensive rat and dilated
cardiomyopathic human hearts. We have recently cloned the gene coding
for myotrophin and expressed it in Escherichia coli. In the
present study, the expression of myotrophin gene was analyzed, and at
least seven transcripts have been detected in rat heart and in other
tissues. We have further analyzed the primary structure of myotrophin
protein and identified significant new structural and functional
domains. Our analysis revealed that one of the ankyrin repeats of
myotrophin is highly homologous specifically to those of
I
Cardiac myocyte cell hypertrophy has been used as an in
vitro model for studying cardiac hypertrophy. Cardiac myocytes
respond to hemodynamic overload by altering the expression of specific
set of genes, which are needed for hypertrophy. Our laboratory has been
studying the molecular basis of myocardial hypertrophy using
spontaneously hypertensive rat as an animal
model(1, 2, 3) . Earlier, Sen et al.(1, 2) isolated a novel 12-kilodalton protein,
which we named myotrophin, from the hypertrophied ventricles of
spontaneously hypertensive rat (1) and dilated cardiomyopathic
human hearts (2) based on its ability to stimulate protein
synthesis specifically in cardiac myocytes(1) . Recently, we
have isolated the cDNA clones encoding rat myotrophin (4) (
Figure 1:
A, distribution of myotrophin mRNAs in
various tissues. H, heart; B, brain; S,
spleen; L, lung; Li, liver; Sk, skeletal
muscle; K, kidney; T, testis. B, Northern
analyses of myotrophin transcripts in 9-day-old WKY hearts. Lane a represents the no-salt buffer-eluted poly(A) RNA, and lane b represents RNA from low salt wash
fraction.
Figure 2:
A,
ankyrin repeats and putative phosphorylation sites for protein kinase C
and casein kinase II are highlighted on the indirectly predicted amino
acid sequence of myotrophin. B, homology of myotrophin ankyrin
repeat 2 to I
The ankyrin repeats of myotrophin span
from amino acid residues 9 to 107 (Fig. 2A). Myotrophin
possesses two full-length ankyrin repeats (repeat 2, 27-58 and
repeat 3, 59-91) and two incomplete (half) repeats (repeat 1,
9-26 and repeat 4, 92-107). One incomplete repeat
(9-26) is a carboxyl half of a typical ankyrin repeat, and the
other (92-107) is an amino half (Fig. 2A).
Ankyrin repeats are generally 33 amino acids in length and possess two
regions: one region is highly conserved and the other is highly
variable. A typical ankyrin repeat sequence is shown below, where X indicates a highly variable region compared with the rest of the
conserved region: XGXTPLHXAXXLLXXGADXXXDX. Since the ankyrin repeats are found in various classes of proteins
(cytoplasmic, nuclear, and cell surface), Hatada et al.(13) have attempted to classify these ankyrin repeats. Based on
the sequence homology in the variable region of these ankyrin repeats,
Hatada et al.(13) have proposed a unique subgroup of
ankyrin repeats for rel and related I It is well known that the I
Figure 3:
Electrophoretic mobility shift assays
analyzing the effect of recombinant myotrophin on the
NF-
To further confirm the myotrophin interaction with NF-
Figure 4:
Electrophoretic mobility shift assays
analyzing the effect of rel-specific p50 and p65 antibodies on
the myotrophin-shifted NF-
In the present study, we have shown that the myotrophin gene
is expressed in various rat tissues and as much as seven
myotrophin-specific transcripts have been detected in rat heart and in
other tissues. These transcripts were most abundant in brain and least
in skeletal muscle compared to other tissues. Based on its ubiquitous
distribution, it appears that the myotrophin protein may be playing a
very important role in the basic functions of various tissues. Our
analysis on the primary structure of the myotrophin protein also
revealed the homology between one of the ankyrin repeats of myotrophin
and to those of I It has been very well
documented that upon exposure to a variety of external stimuli,
NF-
The nucleotide
sequence(s) reported in this paper has been submitted to the
GenBank(TM)/EMBL Data Bank with accession number(s)
U21661[GenBank].
Volume 271,
Number 5,
Issue of February 2, 1996 pp. 2812-2816
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
B Interacting Activity in
Vitro(*)
ABSTRACT
INTRODUCTION
EXPERIMENTAL PROCEDURES
RESULTS
DISCUSSION
FOOTNOTES
ACKNOWLEDGEMENTS
REFERENCES
B
/rel ankyrin repeats. In addition, putative
consensus phosphorylation sites for protein kinase C and casein kinase
II, which were observed in IB proteins, were identified in
myotrophin. To verify the significance of these homologies, B gel
shift assays were performed with Jurkat T cell nuclear extract proteins
and the recombinant myotrophin. Results of these assays indicate that
the recombinant myotrophin has the ability to interact with
NF-B/rel proteins as revealed by the formation of ternary
protein-DNA complexes. While myotrophin-specific antibodies inhibited
the formation of these complexes, rel-specific p50 and p65
antibodies supershifted these complexes. Thus, these results clearly
indicate that the myotrophin protein to be a unique rel/NF-B interacting protein.
)and found that the cardiac myotrophin is
identical to a previously reported rat brain v1 protein (7, 8) whose function is not determined at present in
brain. In addition, we have expressed the myotrophin protein in Escherichia coli and showed that the recombinant myotrophin
has the ability to stimulate protein synthesis in neonatal cardiac
myocytes (4) . In the present study, analyzed the
expression of myotrophin in various tissues, identified new structural
and functional domains, and, using the recombinant myotrophin,
determined one of the key activities of myotrophin.
Northern Analysis of Myotrophin mRNAs
RNA
transcripts specific for myotrophin were analyzed in various rat
tissues. Total RNA was first isolated from 9-day-old rat hearts.
Poly(A)-enriched RNA was isolated using the oligo(dT) method. Briefly,
total RNA was applied to an oligo(dT)-cellulose (Collaborative Research
type III) column at high salt conditions (10 mM Tris-HCl, pH
7.5, 1 mM EDTA, 0.5 M NaCl). After washing the column
with high-salt buffer, poly(A) RNA was eluted with no-salt (10 mM Tris-HCl, pH 7.5, 1 mM EDTA) buffer. The poly(A) RNA
eluted by this method was fractionated on 1% agarose formaldehyde gels,
transferred to a ZetaProbe membrane, and hybridized with radiolabeled
probe. Random-Primer labeling method was used to generate radiolabeled
myotrophin cDNA probe using pCRII-8-Myo cDNA clone (4) . Utilizing the same clone, single-stranded myotrophin-specific
radiolabeled RNA probe was made using T7 RNA polymerase-directed in
vitro transcription system. The hybridization experiment was done
using very high stringency and wash conditions for both the myotrophin
cDNA (42 °C, 5 
SSPE, 10 Denhardt's, 50%
formamide, 2% SDS, and 100 µg/ml salmon sperm DNA) and RNA (50
°C, 1.5 SSPE, 1% SDS, 0.5% BLOTTO, 50% formamide, tRNA (0.2
mg/ml), and salmon sperm DNA (0.5 mg/ml)) probes. Approximately 5
µg of pure poly(A) RNA (lane a in Fig. 1B)
and 2 µg of ``low salt wash RNA'' (lane b in Fig. 1B) from 9-day-old WKY rat hearts was fractionated on the
agarose gel. High stringency hybridization and wash conditions
described above were used to analyze this Northern blot; experiments
were repeated several times with different batches of RNA, and the
results were reproducible. The multiple tissue Northern blot containing
pure poly(A) RNA from various rat tissues was obtained from Clonetech
(no. 7764-1) Approximately 2 µg of pure poly(A) from each tissue
was fractionated on the agarose gel according to Clonetech. The high
stringency hybridization and wash conditions recommended by Clonetech
were used to analyze this multiple tissue Northern blot and is
described above. Poly(A) RNA isolated from various rat tissues in our
laboratory also revealed the same results (data not shown).
Expression of Myotrophin in E. coli
Myotrophin was
expressed in E. coli using the T7 promoter-based vector, pET3a
(Novagen Inc.)(4) . The myotrophin recombinant
pET3a-51 vector was introduced into BL21(DE3) LysS strain, which
harbors a T7 RNA polymerase coding gene. The recombinant myotrophin was
expressed by growing the E. coli cells to early log phase and
was later induced with 0.1 mM isopropyl-1-thio-
-D-galactopyranoside for 16 h.
Overnight induced cells were harvested and lysed in 50 mM Tris-HCl, pH 8.0, 75 mM NaCl by freeze thawing three
times. The lysed E. coli cell debris was removed by
centrifugation at 10,000 g, and the soluble
supernatant was used to purify the recombinant myotrophin. The soluble
form of recombinant myotrophin was highly abundant in the supernatant
and was separated from the rest of the E. coli proteins using
a Centriprep-30 (30-kDa cutoff) Amicon cartridge. Later, the purified
recombinant myotrophin was concentrated using a Centriprep-10 (10-kDa
cutoff) cartridge. On a 12% Tris-Tricine SDS-PAGE, (
)the
purified recombinant myotrophin migrated as a single band at the 12-kDa
region. Protein concentration was estimated using Bio-Rad protein assay
reagent, and appropriate quantities of recombinant myotrophin were used
in gel shift assays. The recombinant myotrophin was further tested for
its immunoreactivity using native myotrophin-specific
antibodies(5) . Native myotrophin-specific antibodies were
generated against a synthetic peptide containing the 17 amino acid
residues of the T26 tryptic peptide of native myotrophin(5) .
Since Western immunoblot analysis clearly showed that the recombinant
myotrophin was immunoreactive to myotrophin-specific antibodies (data
not shown), it was used for functional studies.Electrophoretic Mobility Shift Assays
Phorbol
ester-treated human Jurkat T cell nuclear extract, B, consensus
double-stranded oligonucleotide substrate
(5`-AGTTGAGGGGACTTTCCCAGGC-3`), Oct-1 consensus double-stranded
oligonucleotide substrate (5`-TGTCGAATGCAAATCACTAGAA-3`), and p50 and
p65 supershift antibodies were purchased from Santa Cruz Biotechnology
Inc. Poly(dI-dC)
poly(dIdC) was purchased from Pharmacia
Biotech Inc. Partially purified recombinant
myotrophin(4) and native peptide
myotrophin-specific antibody (1, 2, 3) were
used in the gel shift assays. DNA-protein binding reactions were
carried out in 12 mM HEPES-NaOH (pH 7.9), 4 mM TrisCl (pH 7.9), 60 mM KCl, 1 mM EDTA, and
1 mM dithiothreitol, 2 µg of
poly(dI-dC)poly(dIdC) and 10% glycerol in a final volume of
15 µl. The reactions contained 10 µg of Jurkat cell nuclear
extract, varying amounts (1-3 µl, containing 200 ng/µl)
of bacterially expressed recombinant myotrophin, and 10,000 cpm of
end-labeled NF-B or Oct-1 binding site probe. After incubating at
room temperature for 30 min, the reactions were run on a 4% PAGE using
0.25 TBE as the gel buffer and 1 TBE as the running
buffer. The gel was electrophoresed at 160 volts for 2 h. Later, the
gel was dried and autoradiographed overnight at -70 °C.
Purified myotrophin-specific antibodies (IgG) ((5) ) and
preimmune antibodies (IgG) were preincubated with myotrophin for 1 hour
in ice before the binding reactions were carried out.
Distribution of Myotrophin mRNA in Rat Tissues
A
multiple tissue Northern blot containing poly(A) RNA from various
tissues of rat was obtained from Clonetech. Myotrophin-specific
double-stranded cDNA probe was used to identify myotrophin-specific
transcripts. The blot was hybridized and washed at very high stringency
conditions. The results of the experiment are shown in Fig. 1A. In total, at least five myotrophin-specific
transcripts were detected in these tissues. Among them, two high
molecular weight transcripts (4.3 and 3.5 kb) were detected in almost
all tissues. These transcripts were most abundant in brain and least in
skeletal muscle compared to other tissues. In addition, three
transcripts of 2.4, 1.8, and 1.0 kb in size were also detected in some
tissues, although at different levels. These were detected more
abundantly in certain tissues like testis and liver compared to other
tissues. Based on its ubiquitous distribution, it appears that the
myotrophin protein may be playing a very important role in the basic
functions of various tissues. We have recently obtained several
myotrophin cDNA clones through direct screening of a rat heart
5`-stretch cDNA library (Clonetech), and the preliminary
characterization reveals that the size of the clone inserts correspond
to the sizes of these multiple transcripts. Based on the initial
nucleotide sequence data from few cDNA clones as well as data from
rapid amplification of cDNA ends-polymerase chain reactions (4) , it appears that the heterogeneity in the
length of 3`-untranslated regions contributes to the observed
heterogeneity in the multiple transcripts. The observation of multiple
types of cDNA clones with different 3`-untranslated
regions(4, 8) supports the present
observation of multiple transcripts in the northern hybridization
experiment. Southern analysis of rat genomic DNA also suggests that
myotrophin is coded by a single copy gene as revealed by our
observation of a single 4.3-kilobase pair HindIII genomic DNA
fragment hybridizing to the myotrophin coding region probe, (
)and hence these multiple transcripts arise from the single
copy myotrophin gene. Similar types of multiple transcripts have been
observed for other genes like opsin in mouse, rat, human, and
frog(20) .Myotrophin Gene Expression in Rat Heart
Expression
of myotrophin gene specifically in rat hearts was analyzed in more
detail using Northern blot analysis. Using the coding region of
myotrophin gene, both double-stranded DNA probe (lane a in Fig. 1B) as well as single-stranded antisense RNA probe (lane b in Fig. 1B) was used (see
``Experimental Procedures'') in different Northern blot
experiments. Very high stringency hybridization and wash conditions
were followed for this experiment. Initially, only the 4.3- and 3.5-kb
transcripts were detected when pure poly(A) RNA was used (lane a in Fig. 1B). Since low molecular weight myotrophin
transcripts were not detected significantly in this poly(A) RNA, we
included a low-salt wash step in our oligo(dT) purification procedure
(10 mM Tris-HCl, pH 7.5, 1 mM EDTA, 0.1 M NaCl) before eluting the poly(A) RNA with no-salt buffer. The RNA
from this low salt wash fraction was ethanol precipitated and analyzed
for myotrophin-specific transcripts. Interestingly, the majority of the
myotrophin-specific low molecular weight transcripts (2.4, 1.0, 0.7,
and 0.4 kb) were observed mostly in the low salt-eluted RNA when
compared to pure poly(A) RNA (lane b in Fig. 1B). It is possible that poly(A) tracts in these
transcripts may be either shorter in length or totally devoid of and
thus eluted in the low-salt buffer. The observation of several
myotrophin-specific transcripts in the low salt wash RNA fraction also
suggests that either these are degraded products of the myotrophin
mRNAs after translation or translationally silenced mRNAs ready to be
translated upon receiving the physiological
signal(21, 22) .Primary Structure Analysis of Myotrophin
Protein
The primary structure of the myotrophin protein was
analyzed thoroughly to locate any structural domains that would have
any specific functions. For this purpose, two analyses were conducted.
Initially, using the MacPattern (version 3.2) software and Prosite data
base, the myotrophin amino acid sequence was analyzed to locate any
possible functional domains. This analysis revealed two putative
consensus phosphorylation sites for protein kinase C (TVK) and casein
kinase II (TALE) (Fig. 2A). These putative domains were
not reported earlier for V1 protein from rat
brain(7, 8) . In the second analysis, the individual
ankyrin repeats as well as segments of myotrophin amino acid sequence
were compared against the entire GenBank/EMBL protein data base using
BLASTP program(6) . This analysis revealed new information
about the structural features of myotrophin protein. First, an
additional half ankyrin repeat spanning from residues 92-107 was
identified, which was not reported previously(7, 8) .
During this analysis, a significant homology was also observed between
the ankyrin repeat 2 (residues 27-58) of myotrophin and the
ankyrin repeats of IB proteins (9-12) (Fig. 2B).
B ankyrin repeats. It should be noted that in
addition to rel-associated pp40, the BLASTP analysis
identified other IB members (MAD3, RL/IF-1, and ECI-6) on the
same ankyrin repeats 2 and 4 with similar Poisson
values.
B transcription
factors (9, 10, 11, 12) . The BLASTP
analysis of myotrophin revealed a significant homology between the
ankyrin repeat 2 (residues 27-58) of myotrophin and two ankyrin
repeats of IB proteins (Fig. 2B). The
myotrophin ankyrin repeat 2, in addition to the homology in the core
consensus sequence, possesses homologous residues in the variable
region similar to the IB ankyrin repeat (Fig. 2B). Since the ankyrin repeats are considered as
modular protein-interacting domains with sub-regions of these repeats
conferring unique specificity, the observed homology between myotrophin
ankyrin repeat 2 and the two ankyrin repeats of IB proteins
(9-13) is considered very significant (Fig. 2B). B proteins interact with
NF-B/rel factors through its ankyrin repeats
(15-19). Specifically, it has been shown that IB
ankyrin repeats bind to rel domains of NF-B subunits (p50
and p65). In addition to the ankyrin repeats, putative consensus
phosphorylation sites for protein kinase C and casein kinase II, which
were observed in IB proteins (9-12), were also observed
in myotrophin (Fig. 2A). However, myotrophin is only a
12-kilodalton protein with fewer ankyrin repeats than other known
IB proteins. The observation of IB homologous
ankyrin repeats and putative consensus phosphorylation sites for
protein kinase C and casein kinase II in myotrophin suggested that
myotrophin may be a unique IB-related protein.Electrophoretic Mobility Shift Assays with Recombinant
Myotrophin
Because of the above structural observations,
electrophoretic mobility shift assays (EMSAs) were performed with
Jurkat T cell nuclear extract proteins to identify whether the
NF-B/rel is a target for myotrophin binding. The results
are shown in Fig. 3A. Interestingly, we observed that
with increasing concentrations of myotrophin, ternary complexes are
formed between myotrophin and NF-B/rel. Two types of
ternary complexes (lanes 5-7 in Fig. 3A)
were demonstrated by PAGE. The slower migrating (SC) complexes appear
to be heterotrimeric (myo-NF-B/rel), and the faster
migrating (FC) complexes appear to be devoid of one of the subunits of
the NF-B/rel complex (Fig. 3A).
Furthermore, the preimmune serum IgG (lane 9 in Fig. 3A) did not prevent this binding, whereas the
myotrophin-specific IgG (lane 8 in Fig. 3A)
inhibited specifically the formation of these ternary complexes.
However, myotrophin by itself did not bind to B DNA substrate
probe (lane 4 in Fig. 3A). Unlike other known
IB proteins, myotrophin did not inhibit the DNA binding activity
of the NF-B complex; instead, it formed ternary complexes. These
results were also confirmed by preliminary EMSAs with cardiac myocyte
nuclear extracts (data not shown). To confirm the specificity of
myotrophin interaction with the NF-B/rel complex, Oct-1
EMSAs (14) were also carried out using the same Jurkat T cell
nuclear extract (Fig. 3B). With the same increasing
concentrations of myotrophin, myotrophin (lanes 2-4 in Fig. 3B) did not affect any of the Oct-1DNA
complexes at all. These results clearly show that the specific target
for myotrophin is the subunits of the NF-B/rel complex.
B/rel/B DNA (A) and Oct-1/oct DNA (B) complexes. Phorbol ester-treated Jurkat T cell nuclear
extracts were used as source of NF-B/rel and Oct factors.
Bacterially expressed recombinant myotrophin was added
(``+'' = 1 µl = 200 ng) to the binding
reactions, and its effect was analyzed on 4% PAGE. JNE-P,
phorbol ester-treated Jurkat T cell nuclear extract; B,
radiolabeled B DNA probe; -myo, native
myotrophin-specific antibody IgG(5) ; -p65,
antibody to p65 of NF-B (supershifting); PI, preimmune
serum IgG; Oct, radiolabeled Oct DNA probe; SC,
myotrophin-shifted slower migrating complexes; FC,
myotrophin-shifted faster migrating complexes; NF-B, rel-B heterodimeric protein-DNA
complexes.
B/rel factors, EMSAs were performed in presence of p50 and p65
antibodies. The results are shown in Fig. 4. When incubated with
either p50 (lane 6) or p65 (lane 4) antibodies, the
myotrophin-shifted B complexes were supershifted to slower
migrating ternary complexes (SSC-50 and SSC-65 in Fig. 4), and
the intensity of these complexes increased when more myotrophin was
present in the reaction. These results clearly show that
myotrophin-shifted protein complexes actually contain NF-B/rel factors. It should also be noted that phorbol 12-myristate
13-acetate-induced Jurkat T cells probably contain a sufficient amount
of endogenous myotrophin since myotrophin-shifted B complexes were
also detected at a lower level in the control experiments (lanes 1 and 2 in Fig. 4).
Brel-B DNA
complexes. Phorbol ester-treated Jurkat T cell nuclear extracts were
used as a source of NF-B/rel factors. rel-specific p50 and p65 antibodies were added to the
appropriate B binding reactions. Bacterially expressed recombinant
myotrophin was added (``+'' = 1 µl =
200 ng) to the binding reactions along with appropriate antibodies, and
its effect was analyzed on 4% PAGE. JNE-P, phorbol
ester-treated Jurkat T cell nuclear extract; B,
radiolabeled B DNA probe; myo, recombinant myotrophin; -p65, antibody to p65 of NF-B complex; -p50, antibody to p50 of NF-B complex; SC,
myotrophin-shifted slower migrating complexes; NF-B, rel-B heterodimeric protein-DNA complexes; SSC-50, supershifted complex by -p50; SSC-65,
supershifted complex by -p65.
B/rel ankyrin repeats. Furthermore,
our analysis showed putative consensus phosphorylation sites for
protein kinase C and casein kinase II in myotrophin protein, which were
also observed in IB proteins. The significance of these
homologies were experimentally confirmed with B gel shift assays.
The results of these gel shift assays clearly show that the recombinant
myotrophin has the ability to interact with NF-B/rel proteins in vitro. In vivo experiments are currently
being conducted to further confirm these results. Thus, these results
clearly indicate that the 12-kDa myotrophin protein is a unique rel/NF-B interacting protein.B/rel proteins are involved in the rapid induction of
genes whose products play a central role in the immune responses,
inflammation, and cell
proliferation(15, 16, 17, 18, 19) .
The most obvious characteristic of NF-B is its rapid translocation
from cytoplasm to nucleus in response to extracellular signals. They
are kept dormant in the cytoplasm by the members of the IB family
of proteins. Many signals inactivate the inhibitor IB, thereby
allowing the NF-B to enter nuclei and rapidly induce coordinate
sets of defense-related genes. It is possible that upon exposure to
chronic hemodynamic overload signals, cardiac myocytes respond through
their NF-B rapid response system to alter myocardial gene
expression. In the present preliminary study, we have shown by its
ability to interact with NF-B in vitro that myotrophin is
probably a component of such a rapid response system, which might
influence the transcription of hypertrophy-specific genes. Based on the
present study, we speculate that myotrophin is probably involved in
regulating the expression of hypertrophy-specific genes in the
myocardium through rel factors and B DNA sites. It should
be noted that no transcription regulatory factor has been reported so
far to be involved in cardiac hypertrophy. Further studies are in
progress to determine the exact mechanism of action of myotrophin.
)))
-We thank Vijaya Kandaswamy and David Young for
technical help during this project.
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  B. Das, S. Gupta, A. Vasanji, Z. Xu, S. Misra, and S. Sen Nuclear Co-translocation of Myotrophin and p65 Stimulates Myocyte Growth: REGULATION BY MYOTROPHIN HAIRPIN LOOPS J. Biol. Chem., October 10, 2008; 283(41): 27947 - 27956. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Xiong, E. Liu, Y. Yan, R. T. Silver, F. Yang, I. H. Chen, Y. Chen, S. Verstovsek, H. Wang, J. Prchal, et al. An Unconventional Antigen Translated by a Novel Internal Ribosome Entry Site Elicits Antitumor Humoral Immune Reactions J. Immunol., October 1, 2006; 177(7): 4907 - 4916. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. K. Sen and S. Roy Relief from a heavy heart: redox-sensitive NF-{kappa}B as a therapeutic target in managing cardiac hypertrophy Am J Physiol Heart Circ Physiol, July 1, 2005; 289(1): H17 - H19. [Full Text] [PDF]
|
|
|
|
 |
|
 L. K. Mosavi, T. J. Cammett, D. C. Desrosiers, and Z.-y. Peng The ankyrin repeat as molecular architecture for protein recognition Protein Sci., June 1, 2004; 13(6): 1435 - 1448. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Sarkar, D. W. Leaman, S. Gupta, P. Sil, D. Young, A. Morehead, D. Mukherjee, N. Ratliff, Y. Sun, M. Rayborn, et al. Cardiac Overexpression of Myotrophin Triggers Myocardial Hypertrophy and Heart Failure in Transgenic Mice J. Biol. Chem., May 7, 2004; 279(19): 20422 - 20434. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. O'Brien, I. Loke, J. E. Davies, I. B. Squire, and L. L. Ng Myotrophin in human heart failure J. Am. Coll. Cardiol., August 20, 2003; 42(4): 719 - 725. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. V. McMurray and C. Hillier The rise and fall of myotrophin in heart failure J. Am. Coll. Cardiol., August 20, 2003; 42(4): 726 - 727. [Full Text] [PDF]
|
|
|
|
|
|
M. Taoka, T. Ichimura, A. Wakamiya-Tsuruta, Y. Kubota, T. Araki, T. Obinata, and T. Isobe V-1, a Protein Expressed Transiently during Murine Cerebellar Development, Regulates Actin Polymerization via Interaction with Capping Protein J. Biol. Chem., February 14, 2003; 278(8): 5864 - 5870. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Gupta, N. H. Purcell, A. Lin, and S. Sen Activation of nuclear factor-{kappa}B is necessary for myotrophin-induced cardiac hypertrophy J. Cell Biol., December 23, 2002; 159(6): 1019 - 1028. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Knuefermann, P. Chen, A. Misra, S.-P. Shi, M. Abdellatif, and N. Sivasubramanian Myotrophin/V-1, a Protein Up-regulated in the Failing Human Heart and in Postnatal Cerebellum, Converts NFkappa B p50-p65 Heterodimers to p50-p50 and p65-p65 Homodimers J. Biol. Chem., June 21, 2002; 277(26): 23888 - 23897. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. C. SCHRÖDER, A. KRASKO, R. BATEL, A. SKOROKHOD, S. PAHLER, M. KRUSE, I. M. MÜLLER, and W. E. G. MÜLLER Stimulation of protein (collagen) synthesis in sponge cells by a cardiac myotrophin-related molecule from Suberites domuncula FASEB J, October 1, 2000; 14(13): 2022 - 2031. [Abstract] [Full Text]
|
|
|
|
 |
|
 D. A.M. Norman, M. H. Yacoub, and P. J.R. Barton Nuclear factor NF-{kappa}B in myocardium: developmental expression of subunits and activation by interleukin-1{beta} in cardiac myocytes in vitro Cardiovasc Res, August 1, 1998; 39(2): 434 - 441. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Sil, V. Kandaswamy, and S. Sen Increased Protein Kinase C Activity in Myotrophin-Induced Myocyte Growth Circ. Res., June 15, 1998; 82(11): 1173 - 1188. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Kalra, N. Sivasubramanian, and D. L. Mann Angiotensin II Induces Tumor Necrosis Factor Biosynthesis in the Adult Mammalian Heart Through a Protein Kinase C-Dependent Pathway Circulation, May 7, 2002; 105(18): 2198 - 2205. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
