ArticleMolecular and cellular biology2005
Coordinated regulation of insulin signaling by the protein tyrosine phosphatases PTP1B and TCPTP.
Article in Molecular and cellular biology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.
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Who cites it
92 citing papers in PubMed, 210 citations in OpenAlex.
- Effects of an Encapsulated Fruit and Vegetable Juice Concentrate on Obesity-Induced Systemic Inflammation: A Randomised Controlled Trial.Nutrients · 2017Trial
- The PTPN1/N2 Peptide Inhibitor Achieves Potent, Long-Acting Glycemic Control and Weight-Loss Dual Efficacy in Mice.ACS omega · 2026Article
- Insulin resistance in the 21st century: new takes on an old problem-2025 Diabetes, Diabetes Care, and Diabetologia Expert Forum.Diabetologia · 2026Review
- The role of classical protein tyrosine phosphatases in diabetic kidney disease and therapeutic implications.Journal of biomedical science · 2026Review
- Mechanisms, functions and therapeutic targeting of protein tyrosine phosphatases.Nature reviews. Molecular cell biology · 2026Review
- Mapping of PTP1B, TCPTP, SHP2, and Putative Substrates Reveals Novel Networks in Glomerular Podocytes.Journal of cellular physiology · 2026Article
- Repurposing Fagonia Indica Alkaloids as Allosteric PTP 1B Inhibitors: Computational Profiling and Biochemical Validation.Cell biochemistry and biophysics · 2025Article
- Targeting Protein Tyrosine Phosphatases via PROteolysis-TArgeting Chimeras (PROTACs): Current Developments and Prospects.Molecules (Basel, Switzerland) · 2025Review
- Network Pharmacology, Molecular Docking and Molecular Dynamics Studies to Predict the Molecular Targets and Mechanisms of Action ofPlants (Basel, Switzerland) · 2025Article
- Bioinformatics analysis reveals shared molecular pathways for relationship between ulcerative colitis and primary sclerosing cholangitis.Genomics & informatics · 2025Article
- Unraveling the Mystery of Insulin Resistance: From Principle Mechanistic Insights and Consequences to Therapeutic Interventions.International journal of molecular sciences · 2025Review
- Article
- Development of Novel Phosphonodifluoromethyl-Containing Phosphotyrosine Mimetics and a First-In-Class, Potent, Selective, and Bioavailable Inhibitor of Human CDC14 Phosphatases.Journal of medicinal chemistry · 2024Article
- Site-Specifically Modified Peptide Inhibitors of Protein Tyrosine Phosphatase 1B and T-Cell Protein Tyrosine Phosphatase with Enhanced Stability and Improved In Vivo Long-Acting Activity.ACS pharmacology & translational science · 2024Article
- Review
- Article
- The Impact of ETV6-NTRK3 Oncogenic Gene Fusions on Molecular and Signaling Pathway Alterations.Cancers · 2023Article
- Interplay between EGFR, E-cadherin, and PTP1B in epidermal homeostasis.Tissue barriers · 2023Review
- Engineered allostery in light-regulated LOV-Turbo enables precise spatiotemporal control of proximity labeling in living cells.Nature methods · 2023Article
- A Descriptive Review of the Action Mechanisms of Berberine, Quercetin and Silymarin on Insulin Resistance/Hyperinsulinemia and Cardiovascular Prevention.Molecules (Basel, Switzerland) · 2023Review
32 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
The protein tyrosine phosphatase PTP1B is a negative regulator of insulin signaling and a therapeutic target for type 2 diabetes. Our previous studies have shown that the closely related tyrosine phosphatase TCPTP might also contribute to the regulation of insulin receptor (IR) signaling in vivo (S. Galic, M. Klingler-Hoffmann, M. T. Fodero-Tavoletti, M. A. Puryer, T. C. Meng, N. K. Tonks, and T. Tiganis, Mol. Cell. Biol. 23:2096-2108, 2003). Here we show that PTP1B and TCPTP function in a coordinated and temporally distinct manner to achieve an overall regulation of IR phosphorylation and signaling. Whereas insulin-induced phosphatidylinositol 3-kinase/Akt signaling was prolonged in both TCPTP-/- and PTP1B-/- immortalized mouse embryo fibroblasts (MEFs), mitogen-activated protein kinase ERK1/2 signaling was elevated only in PTP1B-null MEFs. By using phosphorylation-specific antibodies, we demonstrate that both IR beta-subunit Y1162/Y1163 and Y972 phosphorylation are elevated in PTP1B-/- MEFs, whereas Y972 phosphorylation was elevated and Y1162/Y1163 phosphorylation was sustained in TCPTP-/- MEFs, indicating that PTP1B and TCPTP differentially contribute to the regulation of IR phosphorylation and signaling. Consistent with this, suppression of TCPTP protein levels by RNA interference in PTP1B-/- MEFs resulted in no change in ERK1/2 signaling but caused prolonged Akt activation and Y1162/Y1163 phosphorylation. These results demonstrate that PTP1B and TCPTP are not redundant in insulin signaling and that they act to control both common as well as distinct insulin signaling pathways in the same cell.
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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.