ArticlePloS one2013
ERK positive feedback regulates a widespread network of tyrosine phosphorylation sites across canonical T cell signaling and actin cytoskeletal proteins in Jurkat T cells.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 36 citations in OpenAlex.
- Phosphotyrosine proteomics reveals novel Zap70 and Itk pathway targets downstream of TCR and CAR in Jurkat T cells.Scientific reports · 2026Article
- Phosphoproteomic analysis of successive Jurkat CD19-CAR generations reveals TCRζ-driven signalling.Cellular signalling · 2026Article
- The phosphatases TCPTP, PTPN22, and SHP1 play unique roles in T cell phosphotyrosine maintenance and feedback regulation of the TCR.Scientific reports · 2025Article
- Evaluating First-Pass, High Protein Capacity Desalting Techniques For Phosphoproteomics Applications.bioRxiv : the preprint server for biology · 2025Article
- Posttranslational Regulation of Mammalian Sulfur Amino Acid Metabolism.International journal of molecular sciences · 2025Review
- Post-translational modification-centric base editor screens to assess phosphorylation site functionality in high throughput.Nature methods · 2024Article
- Review
- SILAC Phosphoproteomics Reveals Unique Signaling Circuits in CAR-T Cells and the Inhibition of B Cell-Activating Phosphorylation in Target Cells.Journal of proteome research · 2022Article
- Regulatory effects of post-translational modifications on zDHHCThe Journal of biological chemistry · 2020Review
- Targeting Phosphotyrosine in Native Proteins with Conditional, Bispecific Antibody Traps.Journal of the American Chemical Society · 2020Article
- The role of competing mechanisms on Lck regulation.Immunologic research · 2020Review
- The Influence of Reactive Oxygen Species in the Immune System and Pathogenesis of Multiple Sclerosis.Autoimmune diseases · 2020Review
- Fibroblasts Mobilize Tumor Cell Glycogen to Promote Proliferation and Metastasis.Cell metabolism · 2019Article
- G protein subunit phosphorylation as a regulatory mechanism in heterotrimeric G protein signaling in mammals, yeast, and plants.The Biochemical journal · 2018Review
- A PLC-γ1 Feedback Pathway Regulates Lck Substrate Phosphorylation at the T-Cell Receptor and SLP-76 Complex.Journal of proteome research · 2017Article
- HIPK2-T566 autophosphorylation diversely contributes to UV- and doxorubicin-induced HIPK2 activation.Oncotarget · 2017Article
- Quantitative Phosphoproteomic Analysis of T-Cell Receptor Signaling.Methods in molecular biology (Clifton, N.J.) · 2017Article
- Lighting Up T Lymphocyte Signaling with Quantitative Phosphoproteomics.Frontiers in immunology · 2017Review
- Adaptation of HepG2 cells to a steady-state reduction in the content of protein phosphatase 6 (PP6) catalytic subunit.Experimental cell research · 2015Article
- Vav1 Regulates T-Cell Activation through a Feedback Mechanism and Crosstalk between the T-Cell Receptor and CD28.Journal of proteome research · 2015Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Competing positive and negative signaling feedback pathways play a critical role in tuning the sensitivity of T cell receptor activation by creating an ultrasensitive, bistable switch to selectively enhance responses to foreign ligands while suppressing signals from self peptides. In response to T cell receptor agonist engagement, ERK is activated to positively regulate T cell receptor signaling through phosphorylation of Ser(59) Lck. To obtain a wide-scale view of the role of ERK in propagating T cell receptor signaling, a quantitative phosphoproteomic analysis of 322 tyrosine phosphorylation sites by mass spectrometry was performed on the human Jurkat T cell line in the presence of U0126, an inhibitor of ERK activation. Relative to controls, U0126-treated cells showed constitutive decreases in phosphorylation through a T cell receptor stimulation time course on tyrosine residues found on upstream signaling proteins (CD3 chains, Lck, ZAP-70), as well as downstream signaling proteins (VAV1, PLCγ1, Itk, NCK1). Additional constitutive decreases in phosphorylation were found on the majority of identified proteins implicated in the regulation of actin cytoskeleton pathway. Although the majority of identified sites on T cell receptor signaling proteins showed decreases in phosphorylation, Tyr(598) of ZAP-70 showed elevated phosphorylation in response to U0126 treatment, suggesting differential regulation of this site via ERK feedback. These findings shed new light on ERK's role in positive feedback in T cell receptor signaling and reveal novel signaling events that are regulated by this kinase, which may fine tune T cell receptor activation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.