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significance when the coexistence of related proteins is analyzed using func-
tional annotation-based bioinformatic strategies. Often, subtle differences
between experimental conditions may be missed as no individual dramati-
cally modulated factors may present themselves. If, however, we consider
the posit that GPCR signaling functions are indeed composed of multiple
interlaced network activities, the appreciation and functionally relevant cor-
relation of these small changes with each other may illuminate a more real-
istic view of cellular physiology and receptor signaling.
3.3. Posttranslational proteomic analysis
The ability to identify multiple quantitative proteomic effects in response to
GPCR-associated activities, using mass tag or protein labeling approaches,
represents a significant functional advance upon transcriptional profiling, as
the protein gene products are more closely associated with the specific bio-
logical actions studied. However, the true functional status of any protein is
not simply dictated by its expression level but also by the posttranslational
modification (PTM) status of that protein. PTM of proteins creates an extra
functional spectrum to the basic nature of the unmodified protein. While
genomes, transcriptomes, and simple “expression” proteomes in higher spe-
cies (mice, humans) may comprise between 20,000 and 40,000 transcripts/
proteins, the posttranslationally modified proteome could approach easily
1 10 6 “unique” proteins. Therefore, for each protein, nearly hundreds
of differentially modified analogs may exist, each with a subtly varied func-
tionality. The abundance and potential variety of PTM events that can be
applied to proteins (often more than one per protein) generates this enor-
mous functional range.
Approximately, three hundred different types of PTMs have been
reported to date. It is highly likely, however, that additional forms are yet
to be fully characterized. 115 While the basic expression profile of a protein
may control its general functional “potential,” the chemical PTM of a protein
tends to induce a specificity of its function. Almost all proteins undergo one
or other type of PTM during or after their synthesis in a well-defined cellular
location. Within any specific peptide or protein, almost all of its constituent
amino acids, except Leu, Ile, Val, Ala, and Phe, are available for some
form of reversible chemical modification. 116 The diversity of chemical modi-
fications that encompass protein PTMs is extremely high, for example, PTMs
include phosphorylation, glycosylation, oxidation, ubiquitination, methyla-
tion, acetylation, nitrosylation, sulfation, sumoylation, myristoylation, and
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