Early detection and targeted therapy represent a novel regimen of cancer management. The understanding of receptor tyrosine kinases in tumorigenesis at the molecular level has led to the first generation of kinase inhibitors for anticancer therapy that targets a specific kinase or pathway. While the therapeutic advantage is obvious, targeted therapy often relapses and results in drug resistance for advanced cancers. To achieve feasible early detection and better efficacy of therapeutics targeting multiple pathways, significantly more biomarkers and drug targets are in demand, especially for individualized therapy. Recent advances in phosphoprotein enrichment and MS technologies for quantitative phosphoproteome analysis provide great opportunities in the identification and validation of kinases as drug targets. The MS-based phosphoproteomic technologies would be useful tools as well for the identification of phosphosignatures unique to a specific type or subtype of cancer and drug responsive biomarkers. This review summarizes the major kinases acting as cancer biomarkers and drug targets, the advances of MS-based phosphoproteomic technologies, and some potential values and challenges of this emerging phosphoproteomics-based biom...Continue Reading
Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene
Protease-catalyzed incorporation of 18O into peptide fragments and its application for protein sequencing by electrospray and matrix-assisted laser desorption/ionization mass spectrometry
A putative serine/threonine kinase encoding gene BTAK on chromosome 20q13 is amplified and overexpressed in human breast cancer cell lines
Analysis of receptor signaling pathways by mass spectrometry: identification of vav-2 as a substrate of the epidermal and platelet-derived growth factor receptors
Site-specific mass tagging with stable isotopes in proteins for accurate and efficient protein identification
Analysis of protein phosphorylation by a combination of elastase digestion and neutral loss tandem mass spectrometry
Detection of tyrosine phosphorylated peptides by precursor ion scanning quadrupole TOF mass spectrometry in positive ion mode
Quantitative analysis of bacterial and mammalian proteomes using a combination of cysteine affinity tags and 15N-metabolic labeling
Phosphoprotein isotope-coded affinity tag approach for isolating and quantitating phosphopeptides in proteome-wide analyses
Phosphoprotein isotope-coded affinity tags: application to the enrichment and identification of low-abundance phosphoproteins
Stable isotope labeling by amino acids in cell culture, SILAC, as a simple and accurate approach to expression proteomics.
Multiple BCR-ABL kinase domain mutations confer polyclonal resistance to the tyrosine kinase inhibitor imatinib (STI571) in chronic phase and blast crisis chronic myeloid leukemia
A mass spectrometry-based proteomic approach for identification of serine/threonine-phosphorylated proteins by enrichment with phospho-specific antibodies: identification of a novel protein, Frigg, as a protein kinase A substrate.
Quantitation of changes in protein phosphorylation: a simple method based on stable isotope labeling and mass spectrometry
Identification of novel phosphorylation sites on Xenopus laevis Aurora A and analysis of phosphopeptide enrichment by immobilized metal-affinity chromatography.
Large-scale analysis of in vivo phosphorylated membrane proteins by immobilized metal ion affinity chromatography and mass spectrometry.
Phosphoprotein isotope-coded solid-phase tag approach for enrichment and quantitative analysis of phosphopeptides from complex mixtures
Antitumor efficacy of intermittent treatment schedules with the rapamycin derivative RAD001 correlates with prolonged inactivation of ribosomal protein S6 kinase 1 in peripheral blood mononuclear cells
Identification of phosphoproteins and their phosphorylation sites in the WEHI-231 B lymphoma cell line.
Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry
Titania as a chemo-affinity support for the column-switching HPLC analysis of phosphopeptides: application to the characterization of phosphorylation sites in proteins by combination with protease digestion and electrospray ionization mass spectrometry
Selective tyrosine hyperphosphorylation of cytoskeletal and stress proteins in primary human breast cancers: implications for adjuvant use of kinase-inhibitory drugs
A neutral loss activation method for improved phosphopeptide sequence analysis by quadrupole ion trap mass spectrometry
Evaluation of the acid-cleavable isotope-coded affinity tag reagents: application to camptothecin-treated cortical neurons
Selective isolation at the femtomole level of phosphopeptides from proteolytic digests using 2D-NanoLC-ESI-MS/MS and titanium oxide precolumns
Open tubular immobilized metal ion affinity chromatography combined with MALDI MS and MS/MS for identification of protein phosphorylation sites
Improved peptide identification in proteomics by two consecutive stages of mass spectrometric fragmentation
Using immobilized metal affinity chromatography, two-dimensional electrophoresis and mass spectrometry to identify hepatocellular proteins with copper-binding ability
Phosphoproteome analysis of mouse liver using immobilized metal affinity purification and linear ion trap mass spectrometry
Multiplexed protein quantitation in Saccharomyces cerevisiae using amine-reactive isobaric tagging reagents.
Differential mass spectrometry: a label-free LC-MS method for finding significant differences in complex peptide and protein mixtures
Global effects of BCR/ABL and TEL/PDGFRbeta expression on the proteome and phosphoproteome: identification of the Rho pathway as a target of BCR/ABL
Comparative proteome analyses of human plasma following in vivo lipopolysaccharide administration using multidimensional separations coupled with tandem mass spectrometry
Phosphoproteomic analysis using immobilized metal ion affinity chromatography on the basis of cellulose powder
Quantitative proteome analysis of human plasma following in vivo lipopolysaccharide administration using 16O/18O labeling and the accurate mass and time tag approach.
Expression profiling using a tumor-specific cDNA microarray predicts the prognosis of intermediate risk neuroblastomas
Highly selective enrichment of phosphorylated peptides from peptide mixtures using titanium dioxide microcolumns.
Time-resolved mass spectrometry of tyrosine phosphorylation sites in the epidermal growth factor receptor signaling network reveals dynamic modules.
Quantitative phosphoproteome analysis using a dendrimer conjugation chemistry and tandem mass spectrometry
Fe3O4/TiO2 core/shell nanoparticles as affinity probes for the analysis of phosphopeptides using TiO2 surface-assisted laser desorption/ionization mass spectrometry
Approval summary for erlotinib for treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen
Enrichment of phosphorylated proteins and peptides from complex mixtures using metal oxide/hydroxide affinity chromatography (MOAC)
Parts per million mass accuracy on an Orbitrap mass spectrometer via lock mass injection into a C-trap.
Exploring the sounds of silence: RNAi-mediated gene silencing for target identification and validation
An integrated strategy for identification and relative quantification of site-specific protein phosphorylation using liquid chromatography coupled to MS2/MS3
Overexpression of platelet-derived growth factor receptor alpha in endothelial cells of hepatocellular carcinoma associated with high metastatic potential
Analysis of porcine peripheral blood mononuclear cells proteome by 2-DE and MS: analytical and biological variability in the protein expression level and protein identification
Proteomic survey of copper-binding proteins in Arabidopsis roots by immobilized metal affinity chromatography and mass spectrometry
Selective zirconium dioxide-based enrichment of phosphorylated peptides for mass spectrometric analysis
Novel protein phosphorylation site identification in spinach stroma membranes by titanium dioxide microcolumns and tandem mass spectrometry
Quantitative phosphoproteomics of vasopressin-sensitive renal cells: regulation of aquaporin-2 phosphorylation at two sites
Phosphoproteome profiling of human skin fibroblast cells in response to low- and high-dose irradiation
Sorafenib (BAY 43-9006, Nexavar), a dual-action inhibitor that targets RAF/MEK/ERK pathway in tumor cells and tyrosine kinases VEGFR/PDGFR in tumor vasculature
HER2 kinase domain mutation results in constitutive phosphorylation and activation of HER2 and EGFR and resistance to EGFR tyrosine kinase inhibitors
The mammalian target of rapamycin (mTOR) pathway regulates mitochondrial oxygen consumption and oxidative capacity
Kinase domain mutants of Bcr-Abl exhibit altered transformation potency, kinase activity, and substrate utilization, irrespective of sensitivity to imatinib
Multilectin affinity chromatography for characterization of multiple glycoprotein biomarker candidates in serum from breast cancer patients
Zirconium phosphonate-modified porous silicon for highly specific capture of phosphopeptides and MALDI-TOF MS analysis
A probability-based approach for high-throughput protein phosphorylation analysis and site localization
Screening of glycosylation patterns in serum using natural glycoprotein microarrays and multi-lectin fluorescence detection
Self-regulated Plk1 recruitment to kinetochores by the Plk1-PBIP1 interaction is critical for proper chromosome segregation
Elevated levels of phosphorylated fibrinogen-alpha-isoforms and differential expression of other post-translationally modified proteins in the plasma of ovarian cancer patients.
Sorafenib (BAY 43-9006) inhibits tumor growth and vascularization and induces tumor apoptosis and hypoxia in RCC xenograft models
Sorafenib blocks the RAF/MEK/ERK pathway, inhibits tumor angiogenesis, and induces tumor cell apoptosis in hepatocellular carcinoma model PLC/PRF/5
Proteomics analysis of protein kinases by target class-selective prefractionation and tandem mass spectrometry.
Rapid enrichment of phosphopeptides and phosphoproteins from complex samples using magnetic particles coated with alumina as the concentrating probes for MALDI MS analysis
Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry
Analysis of phosphorylation sites on proteins from Saccharomyces cerevisiae by electron transfer dissociation (ETD) mass spectrometry
Relative quantification of stable isotope labeled peptides using a linear ion trap-Orbitrap hybrid mass spectrometer
A novel phosphoprotein analysis scheme for assessing changes in premalignant and malignant breast cell lines using 2D liquid separations, protein microarrays and tandem mass spectrometry
Integration of phosphoproteomic, chemical, and biological strategies for the functional analysis of targeted protein phosphorylation
Two dimensional (pI & ds) separation of phosphorylated proteins by isoelectric focusing/asymmetrical flow field-flow fractionation: application to prostatic cancer cell line
Structure and dynamics of molecular networks: a novel paradigm of drug discovery: a comprehensive review
2,3,5,6-Tetramethylpyrazine of Ephedra sinica regulates melanogenesis and inflammation in a UVA-induced melanoma/keratinocytes co-culture system
Human gene control by vital oncogenes: revisiting a theoretical model and its implications for targeted cancer therapy
Functional Fe3O4@ZnO magnetic nanoparticle-assisted enrichment and enzymatic digestion of phosphoproteins from saliva
Comparison of 2 cell-based phosphoprotein assays to support screening and development of an ALK inhibitor
A novel tantalum-based sol-gel packed microextraction syringe for highly specific enrichment of phosphopeptides in MALDI-MS applications
Phosphoproteomics Reveals Key Regulatory Kinases and Modulated Pathways Associated with Ovarian Cancer Tumors
Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.
Chronic Fatigue Syndrome
Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.
Systemic Juvenile Idiopathic Arthritis
Systemic juvenile idiopathic arthritis is a rare rheumatic disease that affects children. Symptoms include joint pain, but also fevers and skin rashes. Here is the latest on this disease.
Chromatin Regulation and Circadian Clocks
The circadian clock plays an important role in regulating transcriptional dynamics through changes in chromatin folding and remodelling. Discover the latest research on Chromatin Regulation and Circadian Clocks here.
Central Pontine Myelinolysis
Central Pontine Myelinolysis is a neurologic disorder caused most frequently by rapid correction of hyponatremia and is characterized by demyelination that affects the central portion of the base of the pons. Here is the latest research on this disease.
Myocardial stunning is a mechanical dysfunction that persists after reperfusion of previously ischemic tissue in the absence of irreversible damage including myocardial necrosis. Here is the latest research.
Pontocerebellar hypoplasias are a group of neurodegenerative autosomal recessive disorders with prenatal onset, atrophy or hypoplasia of the cerebellum, hypoplasia of the ventral pons, microcephaly, variable neocortical atrophy and severe mental and motor impairments. Here is the latest research on pontocerebellar hypoplasia.
Cell Atlas Along the Gut-Brain Axis
Profiling cells along the gut-brain axis at the single cell level will provide unique information for each cell type, a three-dimensional map of how cell types work together to form tissues, and insights into how changes in the map underlie health and disease of the GI system and its crosstalk with the brain. Disocver the latest research on single cell analysis of the gut-brain axis here.
Chronic Traumatic Encephalopathy
Chronic Traumatic Encephalopathy (CTE) is a progressive degenerative disease that occurs in individuals that suffer repetitive brain trauma. Discover the latest research on traumatic encephalopathy here.