Mass Spectrometric Contributions to the Practice of Phosphorylation Site Mapping through 2003

Reversible phosphorylation of proteins is among the most important post-translational modifications, and elucidation of sites of phosphorylation is essential to understanding the regulation of key cellular processes such as signal transduction. Unfortunately phosphorylation site mapping is as technically challenging as it is important. Limitations in the traditional method of Edman degradation of 32P-labeled phosphoproteins have spurred the development of mass spectrometric methods for phosphopeptide identification and sequencing. To assess the practical contributions of the various technologies we conducted a literature search of publications using mass spectrometry to discover previously unknown phosphorylation sites. 1281 such phosphorylation sites were reported in 203 publications between 1992 and 2003. This review examines and catalogues those methods, identifies the trends that have emerged in the past decade, and presents representative examples from among these methods.

[1]  D. Müller-Wieland,et al.  Identification of major tyrosine phosphorylation sites in the human insulin receptor substrate Gab-1 by insulin receptor kinase in vitro. , 2000, Biochemistry.

[2]  S. Gygi,et al.  Absolute quantification of proteins and phosphoproteins from cell lysates by tandem MS , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[3]  S. Carr,et al.  Phosphopeptide/phosphoprotein mapping by electron capture dissociation mass spectrometry. , 2001, Analytical chemistry.

[4]  Lance Wells,et al.  Mapping Sites of O-GlcNAc Modification Using Affinity Tags for Serine and Threonine Post-translational Modifications* , 2002, Molecular & Cellular Proteomics.

[5]  M. Wilm,et al.  Analytical properties of the nanoelectrospray ion source. , 1996, Analytical chemistry.

[6]  J. Porath,et al.  Isolation of phosphoproteins by immobilized metal (Fe3+) affinity chromatography. , 1986, Analytical biochemistry.

[7]  S. Carr,et al.  N-Terminal peptide labeling strategy for incorporation of isotopic tags: a method for the determination of site-specific absolute phosphorylation stoichiometry. , 2002, Rapid communications in mass spectrometry : RCM.

[8]  F. Carrier,et al.  Phosphorylation regulates nucleophosmin targeting to the centrosome during mitosis as detected by cross-reactive phosphorylation-specific MKK1/MKK2 antibodies. , 2004, The Biochemical journal.

[9]  J. Yates,et al.  A method for the comprehensive proteomic analysis of membrane proteins , 2003, Nature Biotechnology.

[10]  Veeranna,et al.  Characterization of the phosphorylation sites of human high molecular weight neurofilament protein by electrospray ionization tandem mass spectrometry and database searching. , 1998, Biochemistry.

[11]  X. Yao,et al.  Proteolytic 18O labeling for comparative proteomics: model studies with two serotypes of adenovirus. , 2001, Analytical chemistry.

[12]  J. Shabanowitz,et al.  Phosphoproteome Analysis of Capacitated Human Sperm , 2003, The Journal of Biological Chemistry.

[13]  S. Carr,et al.  Selective detection and sequencing of phosphopeptides at the femtomole level by mass spectrometry. , 1996, Analytical biochemistry.

[14]  J. Crespo,et al.  Quantitation of changes in protein phosphorylation: A simple method based on stable isotope labeling and mass spectrometry , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[15]  N. Packer,et al.  Protein phosphorylation: technologies for the identification of phosphoamino acids. , 1998, Journal of chromatography. A.

[16]  Z. Darżynkiewicz.  Flow cytometric methods for RNA content analysis , 1991 .

[17]  J. Shabanowitz,et al.  Peptide and protein sequence analysis by electron transfer dissociation mass spectrometry. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[18]  E. Krause,et al.  Derivatization of phosphorylated peptides with S- and N-nucleophiles for enhanced ionization efficiency in matrix-assisted laser desorption/ionization mass spectrometry. , 2004, Rapid communications in mass spectrometry : RCM.

[19]  S. Dowdy,et al.  2-D phosphopeptide mapping. , 1999, Methods in molecular biology.

[20]  J. Stults,et al.  Electrospray ionization mass spectrometry of phosphopeptides isolated by on-line immobilized metal-ion affinity chromatography , 1993, Journal of the American Society for Mass Spectrometry.

[21]  S. Carr,et al.  A multidimensional electrospray MS-based approach to phosphopeptide mapping. , 2001, Analytical chemistry.

[22]  M. Sussman,et al.  An isotope labeling strategy for quantifying the degree of phosphorylation at multiple sites in proteins , 2004, Journal of the American Society for Mass Spectrometry.

[23]  R A Bradshaw,et al.  O-Sulfonation of Serine and Threonine , 2004, Molecular & Cellular Proteomics.

[24]  A. Burlingame,et al.  Factors governing the solubilization of phosphopeptides retained on ferric NTA IMAC beads and their analysis by MALDI TOFMS , 2002, Journal of the American Society for Mass Spectrometry.

[25]  B. Sefton.  Measurement of stoichiometry of protein phosphorylation by biosynthetic labeling. , 1991, Methods in enzymology.

[26]  D. Mccormick.  Sequence the Human Genome , 1986, Bio/Technology.

[27]  T. Hunter,et al.  Protein kinases and phosphatases: The Yin and Yang of protein phosphorylation and signaling , 1995, Cell.

[28]  H. Pant,et al.  Characterization of the phosphorylation sites of the squid (Loligo pealei) high‐molecular‐weight neurofilament protein from giant axon axoplasm , 2001, Journal of neurochemistry.

[29]  J. A. Nimmo,et al.  The identification of phosphoseryl residues during the determination amino acid sequence in phosphoproteins. , 1982, Analytical biochemistry.

[30]  A. Pandey,et al.  Detection of tyrosine phosphorylated peptides by precursor ion scanning quadrupole TOF mass spectrometry in positive ion mode. , 2001, Analytical chemistry.

[31]  Hanno Steen,et al.  Analysis of protein phosphorylation using mass spectrometry: deciphering the phosphoproteome. , 2002, Trends in biotechnology.

[32]  N. Ahn,et al.  Protein phosphorylation analysis by electrospray ionization-mass spectrometry. , 1997, Methods in enzymology.

[33]  A. Hinnebusch,et al.  Identification of phosphorylation sites in proteins separated by polyacrylamide gel electrophoresis. , 1998, Analytical chemistry.

[34]  L. Hood,et al.  Solid-phase sequencing of 32P-labeled phosphopeptides at picomole and subpicomole levels. , 1991, Methods in enzymology.

[35]  T. Hunter,et al.  Phosphopeptide mapping and phosphoamino acid analysis by electrophoresis and chromatography on thin‐layer cellulose plates , 1994, Electrophoresis.

[36]  Thomas A Neubert,et al.  ABRF-PRG03: phosphorylation site determination. , 2003, Journal of biomolecular techniques : JBT.

[37]  M. J. Chalmers,et al.  Protein kinase A phosphorylation characterized by tandem Fourier transform ion cyclotron resonance mass spectrometry , 2004, Proteomics.

[38]  M. Byford.  Rapid and selective modification of phosphoserine residues catalysed by Ba2+ ions for their detection during peptide microsequencing. , 1991, The Biochemical journal.

[39]  James C. Marsters,et al.  Selective Detection of Membrane Proteins Without Antibodies , 2002, Molecular & Cellular Proteomics.

[40]  Steven P Gygi,et al.  Phosphoproteomic Analysis of the Developing Mouse Brain*S , 2004, Molecular & Cellular Proteomics.

[41]  A. Sickmann,et al.  Phosphoamino acid analysis , 2001, Proteomics.

[42]  L. Heilmeyer,et al.  Sequence analysis of phosphoserine‐containing peptides , 1986, FEBS letters.

[43]  H. Wenschuh,et al.  Phosphopeptide analysis by positive and negative ion matrix-assisted laser desorption/ionization mass spectrometry. , 2001, Rapid communications in mass spectrometry : RCM.

[44]  J. V. Moran,et al.  Initial sequencing and analysis of the human genome. , 2001, Nature.

[45]  Richard D. Smith,et al.  Phosphoprotein isotope-coded affinity tag approach for isolating and quantitating phosphopeptides in proteome-wide analyses. , 2001, Analytical chemistry.

[46]  C. Bertozzi,et al.  Tyrosine sulfation: a modulator of extracellular protein-protein interactions. , 2000, Chemistry & biology.

[47]  F. Regnier,et al.  An isotope coding strategy for proteomics involving both amine and carboxyl group labeling. , 2002, Methods in molecular biology.

[48]  M. Bollen,et al.  Protein phosphorylation and protein phosphatases De Panne, Belgium, September 19–24, 1999 , 2000, The EMBO journal.

[49]  F. McLafferty,et al.  Electron Capture Dissociation of Multiply Charged Protein Cations. A Nonergodic Process , 1998 .

[50]  A. Pandey,et al.  A proteomic approach for quantitation of phosphorylation using stable isotope labeling in cell culture. , 2003, Analytical chemistry.

[51]  M. Wilm,et al.  Nano electrospray combined with a quadrupole ion trap for the analysis of peptides and protein digests , 1996, Journal of the American Society for Mass Spectrometry.

[52]  J. Gebler,et al.  Selective analysis of phosphopeptides within a protein mixture by chemical modification, reversible biotinylation and mass spectrometry. , 2001, Rapid communications in mass spectrometry : RCM.

[53]  M. Sussman,et al.  Mass Spectrometric Resolution of Reversible Protein Phosphorylation in Photosynthetic Membranes ofArabidopsis thaliana* , 2001, The Journal of Biological Chemistry.

[54]  P. Roach,et al.  Identification of phosphorylation sites in peptides using a microsequencer. , 1991, Methods in enzymology.

[55]  Emanuel F Petricoin,et al.  Signal pathway profiling of ovarian cancer from human tissue specimens using reverse‐phase protein microarrays , 2003, Proteomics.

[56]  D. Stone,et al.  Differential phosphoproteome profiling by affinity capture and tandem matrix‐assisted laser desorption/ionization mass spectrometry , 2004, Proteomics.

[57]  O. Fiehn,et al.  Comparative quantification and identification of phosphoproteins using stable isotope labeling and liquid chromatography / mass spectrometry , 2022 .

[58]  Kelvin H. Lee,et al.  A two‐dimensional electrophoresis map of Chinese hamster ovary cell proteins based on fluorescence staining , 2004, Electrophoresis.

[59]  T. Hunter,et al.  Phosphopeptide mapping and phosphoamino acid analysis by two-dimensional separation on thin-layer cellulose plates. , 1991, Methods in enzymology.

[60]  Richard D. Smith,et al.  Phosphoprotein isotope-coded solid-phase tag approach for enrichment and quantitative analysis of phosphopeptides from complex mixtures. , 2003, Analytical chemistry.

[61]  Wayne F. Patton,et al.  Characterization of dynamic and steady‐state protein phosphorylation using a fluorescent phosphoprotein gel stain and mass spectrometry , 2004, Electrophoresis.

[62]  T. Hunter,et al.  Signaling—2000 and Beyond , 2000, Cell.

[63]  Angela Bachi,et al.  Analysis of Protein Phosphorylation by Mass Spectrometry , 2004, European journal of mass spectrometry.

[64]  M. Posewitz,et al.  Immobilized gallium(III) affinity chromatography of phosphopeptides. , 1999, Analytical chemistry.

[65]  F. Cross,et al.  Accurate quantitation of protein expression and site-specific phosphorylation. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[66]  J. Brüning,et al.  Identification of tyrosine phosphorylation sites in human Gab-1 protein by EGF receptor kinase in vitro. , 1999, Biochemistry.

[67]  I. Chu,et al.  Unique scanning capabilities of a new hybrid linear ion trap mass spectrometer (Q TRAP) used for high sensitivity proteomics applications , 2003, Proteomics.

[68]  Wayne F. Patton,et al.  Detection of phosphoproteins on electroblot membranes using a small‐molecule organic fluorophore , 2004, Electrophoresis.

[69]  J. Shabanowitz,et al.  Phosphoproteome analysis by mass spectrometry and its application to Saccharomyces cerevisiae , 2002, Nature Biotechnology.

[70]  B. Chait,et al.  Enrichment analysis of phosphorylated proteins as a tool for probing the phosphoproteome , 2001, Nature Biotechnology.