Signaling pathways driven by protein and lipid kinases are altered in most human diseases. Therefore, pharmacological inhibitors of cell signaling are one of the most intensively pursued therapeutic approaches for the treatment of diseases such as cancer, neurodegeneration, and metabolic syndromes. Phosphoproteomics is a technique that measures the products of kinase activities and, with the appropriate bioinformatics techniques, the methodology can also provide measures of kinase pathway activation and network circuitry. Hence, due to recent technological advantages, LC-MS-based quantitative phosphoproteomics provides relevant information for the design and implementation of kinase inhibitor based therapies. Here, we review how phosphoproteome profiling is being used in translational research as a means to identify drug targets and biomarkers for personalizing therapies based on kinase inhibitors.
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http://dx.doi.org/10.1002/pmic.201600235 | DOI Listing |
Nat Commun
January 2025
Center for Integrative Genomics, University of Lausanne, Faculty of Biology and Medicine, Lausanne, Switzerland.
The energetic demands of proliferating cells during tumorigenesis require close coordination between the cell cycle and metabolism. While CDK4 is known for its role in cell proliferation, its metabolic function in cancer, particularly in triple-negative breast cancer (TNBC), remains unclear. Our study, using genetic and pharmacological approaches, reveals that CDK4 inactivation only modestly impacts TNBC cell proliferation and tumor formation.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, USA.
Introduction: Type 2 diabetes increases the risk of Alzheimer's disease (AD) dementia. Insulin signaling dysfunction exacerbates tau protein phosphorylation, a hallmark of AD pathology. However, the comprehensive impact of diabetes on patterns of AD-related phosphoprotein in the human brain remains underexplored.
View Article and Find Full Text PDFJ Hazard Mater
December 2024
Department of Veterinary Surgery, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China. Electronic address:
Long-term exposure to high ammonia concentrations could severely impact chicken health. On the other hand, luteolin has been shown to protect against ammonia poisoning. Although phosphorylation is critically involved in toxicity induction, the specific role of phosphorylated proteins in ammonia poisoning remains unclear.
View Article and Find Full Text PDFCell Rep
December 2024
Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599, USA; Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA. Electronic address:
The molecular underpinnings of high-grade endometrial carcinoma (HGEC) metastatic growth and survival are poorly understood. Here, we show that ascites-derived and primary tumor HGEC cell lines in 3D spheroid culture faithfully recapitulate key features of malignant peritoneal effusion and exhibit fundamentally distinct transcriptomic, proteomic, and metabolomic landscapes compared with conventional 2D monolayers. Using a genetic screening platform, we identify MAPK14 (which encodes the protein kinase p38α) as a specific requirement for HGEC in spheroid culture.
View Article and Find Full Text PDFBrain
December 2024
Lab of Parkinson's & Other Movement Disorders, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS); Parkinson's Disease and Movement Disorders Unit, Neurology Service, Hospital Clínic de Barcelona; Institut de Neurociències, Universitat de Barcelona; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) CB06/05/0018-ISCIII; ES 08036 Barcelona, Spain.
Leucine-rich repeat kinase 2 (LRRK2) inhibition is a promising disease-modifying therapy for LRRK2-associated Parkinson's disease (L2PD) and idiopathic PD (iPD). However, pharmaco-dynamic readouts and progression biomarkers for clinical trials aiming for disease modification are insufficient since no endogenous marker reflecting enhanced kinase activity of the most common LRRK2 G2019S mutation has been reported yet in L2PD patients. Employing phospho-/proteomic analyses we assessed the impact that LRRK2 activating mutations had in peripheral blood mononuclear cells (PBMCs) from a LRRK2 clinical cohort from Spain (n=174).
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