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Proteomics and Phosphoproteomics
The completion of the human genome project has brought
us another step closer to understanding some of the most complex cellular
processes, including those occurring as a part of normal cell function
and those involved in progression to disease. In this ‘post-genome
era’, the next step for researchers is to investigate the interactions
among the proteins coded by the genome. While the genome forms the basis
for the processes that the cell executes, it is the dynamism of its protein
products that truly directs and elicits cellular behavior.
The emerging field of proteomics seeks to understand the
dynamics of protein cross-talk, protein-protein interactions, and post-translational
modifications, especially as they relate to cellular phenotypic alterations.
Proteomics has the potential to become a powerful tool in unraveling intricate
cellular systems in a variety of fields, and this exciting and promising
technology may soon become one of the mainstays of biological analysis.
Advances in 2-dimensional gel electrophoresis and mass
spectrometry, the rapid growth of DNA and protein databases in combination
with the development of bioinformatics tools make possible the proteome-wide
analysis of protein expression patterns and their functional relationships.
In collaboration with the UC Proteomics Core Facility,
we hope to grasp the cardiac proteome, and understand the changes that
lead to heart disease.
Figure
1. Two-Dimensional Autoradiogram Demonstrating Phosphorylation Differences
Between WT and Phospholamban KO mice.
Our laboratory
utilizes proteomics to understand broad changes that occur in cardiac
protein expression in several transgenic and gene-targeted mouse models.
In a previous study, we reported that ablation of the phospholamban gene
results an alteration in the expression of over one-hundred other proteins
which contributed to maintaining the hyperdynamic state of the cell. Several
examples are shown below.
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Proteins Upregulated >2-fold in PLN-KO
ventricle. |
ID # |
Accession |
E
pI |
D
pI |
E
MW |
D
MW |
DE
KO/WT |
|
Acyl-CoA
Dehydrogenase, Medium Chain
Acyl-CoA
Dehydrogenase, Short Chain
Antioxidant
Protein 2
ATP Synthase,
Beta Chain
Electron
Transfer Flavoprotein Alpha
Fatty
Acid-Binding Protein, Adipocyte
Fumarate
Hydratase 1
Myoglobin
Myosin
Regulatory Light Chain 1, Ventricle Form
Myosin
Regulatory Light Chain 2
Peroxiredoxin
Stress-70
protein, Mitochondrial Precursor
Superoxide
Dismutase
Tropomyosin 1,
Alpha Chain
|
P45376
Q07417
O08709
P56480
Q99LC5V
P04117
gi/20831568
P04247
P09542
P51667
Q61171
P38647
P09671
P58771 |
ACDM
ACDS
AOP2
ATPB
ETFA
FABA
XM_129612
MYG
MLEV
MLRV
PDX2
GR75
SODM
TPM1 |
7.35
8.01
6.09
5.42
8.75
8.61
7.57
7.40
8.56
4.83
5.01
5.30
5.61
4.73 |
8.6
8.96
5.72
5.19
8.67
8.63
7.75
7.23
9.11
4.71
5.20
5.91
8.80
4.69 |
32.9
42.3
12.7
52.0
63.7
9.3
68.3
14.8
8.4
7.4
16.2
44.8
17.1
18.0
|
46.5
44.9
24.7
56.3
34.9
14.5
50.0
16.9
5.0
18.7
21.8
73.5
24.6
32.7 |
2.678
33.7
2.4530
3.618
3.49
2.578
4.305
13.452
5.324
3.377
3.874
3.02
14.285
9.061 |
|
Proteins Downregulated >2-fold in PLN-KO
ventricle. |
ID # |
Accession |
E
pI |
D
pI |
E
MW |
D
MW |
DE
KO/WT |
|
ATP Synthase,
Alpha Chain
Beta Enolase
Creatine
Kinase, M Chain
Fructose-Bisphosphate
Aldolase A
Isocitrate
Dehydrogenase
Myosin Regulatory
Light Chain 1, Atrial Form
Pyruvate
Dehydrogenase E1 Component
Serum Albumin
Precursor
Troponin T,
Cardiac Muscle Isoform
Tubulin
Alpha-2 Chain
Ubiquinol-Cytochrome C Reductase
Iron-Sulfur Subunit
|
Q28480
P21550
P30275
P05064
P54071
P09541
P65486
P07724
P50752
P48428
P20786
|
ATPA
ENOB
KCRU
ALFA
IDHP
MLEF
ODPA
ALBU
TRT2
TBCA
UCR1 |
7.85
6.58
7.60
8.64
8.50
4.80
7.13
5.57
5.36
6.26
6.52 |
9.22
6.81
8.39
8.40
8.89
5.02
8.49
5.75
4.98
5.25
25.0 |
76.5
69.7
30.1
54.4
51.6
18.2
60.9
59.8
36.6
13.9
5.75 |
59.7
48.9
46.9
39.2
58.7
16.9
43.2
68.6
35.7
12.6
27.7 |
0.385
0.416
0.19
0.49
0.489
0.351
0.385
0.451
0.366
0.683
0.269 |
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The power of proteomics lies in its ability
to provide a broad perspective of alterations in cell physiology and will
continue to provide new leads for cardiovascular research.
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