Biology Reference
In-Depth Information
proteins resulted in localization of phosphorylation sites in dynami-
cally flexible intradomain loops.
Ultimately, phosphoproteomic studies aim to reveal how informa-
tion is transmitted in a signaling pathway, and in some instances the
extent of phosphorylation may be of critical importance. For that
purpose, several methods have been developed for quantification of
site-specific phosphorylation: relative quantification using stable isotope
labeling (PhIAT) [104] or a native reference peptide from the modified
protein [53] as well as absolute quantification [53,56] by external addi-
tion of an isotope analog of the phosphopeptide [56]. Because of its
extreme importance in many biological processes, quantification of
site-specific protein phosphorylation continues to be an area of active
research [105].
OTHER POSTTRANSLATIONAL MODIFICATIONS
Besides phosphorylation, a host of other posttranslational modifications
can regulate the activity of proteins. Because of the immense interest in
these modification events, numerous proteomics-based methods have
been devised to identify proteins containing modifications. Global
analyses of sumoylation [106], ubiquitination [107], and N-linked gly-
coproteins [108] have been published recently.
Eventually, global strategies of analysis will address detection of
posttranslational modifications that dynamically regulate each other.
For example, b-linked N-acetylglucosamine (O-GlcNAc) is a dynamic
posttranslational modification that might be involved in antagonizing
the functional effect of phosphorylation [109]. Khidekel et al. [110]
devised a method that will selectively label and enrich O-GlcNAc
glycosylated proteins for further purification from brain tissue.
Though this method will help study O-GlcNAc modification, clearly,
new methods are needed to address the dynamic interplay between
posttranslational modifications at the global level.
Mass Spectrometry in Medicine
Molecular medicine is one of the major disciplines where systems
biology can be applied [111]. Two classes of specimens are available
for molecular medicine studies: body fluids and human tissues, often
in very limited amounts (for example, obtained from biopsies).
Organization in multicellular environments of tissues brings another
level of complexity for parameters detectable by omics technologies
and in particular mass spectrometry. However, recent developments of
mass spectrometry support integration of these technologies in routine
clinical analysis with tremendous value for medical diagnostics [112].
Caprioli and colleagues pioneered direct tissue profiling by mass
spectrometry by adapting MALDI-TOF technology. Imaging of tissue
sections comprises two steps: (i) thorough interrogation of a grid of
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