ArticleThe EMBO journal2000
A phosphotyrosine displacement mechanism for activation of Src by PTPalpha.
Article in The EMBO journal, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
102 citing papers in PubMed, 235 citations in OpenAlex.
- The role of classical protein tyrosine phosphatases in diabetic kidney disease and therapeutic implications.Journal of biomedical science · 2026Review
- Article
- Activated Src kinase promotes cell cannibalism in Drosophila.The Journal of cell biology · 2023Article
- Article
- Clustering of phosphatase RPTPα promotes Src signaling and the arthritogenic action of synovial fibroblasts.Science signaling · 2023Article
- Glucose-mediated N-glycosylation of RPTPα affects its subcellular localization and Src activation.Oncogene · 2023Article
- Does a rare mutation in PTPRA contribute to the development of Parkinson's disease in an Australian multi-incident family?PloS one · 2022Article
- Article
- Protein tyrosine phosphatases in cell adhesion.The Biochemical journal · 2021Review
- Light-regulated allosteric switch enables temporal and subcellular control of enzyme activity.eLife · 2020Article
- Protein tyrosine phosphatase-α amplifies transforming growth factor-β-dependent profibrotic signaling in lung fibroblasts.American journal of physiology. Lung cellular and molecular physiology · 2020Article
- Protein Arginine Methyltransferase 1 (PRMT1) Selective Inhibitor, TC-E 5003, Has Anti-Inflammatory Properties in TLR4 Signaling.International journal of molecular sciences · 2020Article
- PTPRA Phosphatase Regulates GDNF-Dependent RET Signaling and Inhibits the RET Mutant MEN2A Oncogenic Potential.iScience · 2020Article
- Regulation of the firing activity by PKA-PKC-Src family kinases in cultured neurons of hypothalamic arcuate nucleus.Journal of neuroscience research · 2020Article
- Receptor protein tyrosine phosphatases control Purkinje neuron firing.Cell cycle (Georgetown, Tex.) · 2020Article
- Protein tyrosine phosphatases: promising targets in pancreatic ductal adenocarcinoma.Cellular and molecular life sciences : CMLS · 2019Review
- A Global Analysis of the Receptor Tyrosine Kinase-Protein Phosphatase Interactome.Molecular cell · 2017Article
- Alcohol-dependent molecular adaptations of the NMDA receptor system.Genes, brain, and behavior · 2017Review
- Helicobacter pylori VacA, acting through receptor protein tyrosine phosphatase α, is crucial for CagA phosphorylation in human duodenum carcinoma cell line AZ-521.Disease models & mechanisms · 2016Article
- Regulation of pulmonary endothelial barrier function by kinases.American journal of physiology. Lung cellular and molecular physiology · 2016Review
42 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Protein tyrosine phosphatase alpha (PTPalpha) is believed to dephosphorylate physiologically the Src proto-oncogene at phosphotyrosine (pTyr)527, a critical negative-regulatory residue. It thereby activates Src, and PTPalpha overexpression neoplastically transforms NIH 3T3 cells. pTyr789 in PTPalpha is constitutively phosphorylated and binds Grb2, an interaction that may inhibit PTPalpha activity. We show here that this phosphorylation also specifically enables PTPalpha to dephosphorylate pTyr527. Tyr789-->Phe mutation abrogates PTPalpha-Src binding, dephosphorylation of pTyr527 (although not of other substrates), and neoplastic transformation by overexpressed PTPalpha in vivo. We suggest that pTyr789 enables pTyr527 dephosphorylation by a pilot binding with the Src SH2 domain that displaces the intramolecular pTyr527-SH2 binding. Consistent with model predictions, we find that excess SH2 domains can disrupt PTPalpha-Src binding and can block PTPalpha-mediated dephosphorylation and activation in proportion to their affinity for pTyr789. Moreover, we show that, as predicted by the model, catalytically defective PTPalpha has reduced Src binding in vivo. The displacement mechanism provides another potential control point for physiological regulation of Src-family signal transduction pathways.
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What OpenQuestion holds
Registered trials
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.