Quantitative phosphoproteomics by mass spectrometry: past, present, and future.
Protein phosphorylation-mediated signaling networks regulate much of the cellular response to external stimuli, and dysregulation in these networks has been linked to multiple disease states. Significant advancements have been made over the past decade to enable the analysis and quantification of cellular protein phosphorylation events, but comprehensive analysis of the phosphoproteome is still lacking, as is the ability to monitor signaling at the network level while comprehending the biological implications of each phosphorylation site. In this review we highlight many of the technological advances over the past decade and describe some of the latest applications of these tools to uncover signaling networks in a variety of biological settings. We finish with a concise discussion of the future of the field, including additional advances that are required to link protein phosphorylation analysis with biological insight.
Nita-Lazar
Aleksandra
A
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Saito-Benz
Hideshiro
H
White
Forest M
FM
D000818:Animals; D055808:Drug Discovery / Q000379:methods; D066246:ErbB Receptors / Q000502:physiology; D005544:Forecasting; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D010750:Phosphoproteins / Q000032:analysis* / Q000502:physiology; D010766:Phosphorylation; D040901:Proteomics / Q000379:methods* / Q000639:trends; D015203:Reproducibility of Results; D015398:Signal Transduction; D049490:Systems Biology
D010750:Phosphoproteins; D066246:ErbB Receptors