ArticleMolecular and cellular biology2003
Regulation of insulin receptor signaling by the protein tyrosine phosphatase TCPTP.
Article in Molecular and cellular biology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 175 citations in OpenAlex.
- 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
- Genome-wide CRISPR Screen Identifies Sec31A as a Key Regulator of Alpha Cell Survival.Nature communications · 2025Article
- Protein tyrosine phosphatase 1B in metabolic and cardiovascular diseases: from mechanisms to therapeutics.Frontiers in cardiovascular medicine · 2024Review
- Immunotherapeutic implications of negative regulation by protein tyrosine phosphatases in T cells: the emerging cases of PTP1B and TCPTP.Frontiers in medicine · 2024Review
- Methyl Syringate Stimulates Glucose Uptake by Inhibiting Protein Tyrosine Phosphatases Relevant to Insulin Resistance.Life (Basel, Switzerland) · 2023Article
- The Role of Oxidative Inactivation of Phosphatase PTEN and TCPTP in Fatty Liver Disease.Antioxidants (Basel, Switzerland) · 2023Review
- PTPN2 in the Immunity and Tumor Immunotherapy: A Concise Review.International journal of molecular sciences · 2022Review
- Human Protein Tyrosine Phosphatase 1B (PTP1B): From Structure to Clinical Inhibitor Perspectives.International journal of molecular sciences · 2022Review
- Terminalin from African Mango (Biomolecules · 2022Article
- Analysis of Three Architectures for Controlling PTP1B with Light.ACS synthetic biology · 2022Article
- The catalytic activity of TCPTP is auto-regulated by its intrinsically disordered tail and activated by Integrin alpha-1.Nature communications · 2022Article
- Astragalus mongholicus powder, a traditional Chinese medicine formula ameliorate type 2 diabetes by regulating adipoinsular axis in diabetic mice.Frontiers in pharmacology · 2022Article
- Insulin signaling in AgRP neurons regulates meal size to limit glucose excursions and insulin resistance.Science advances · 2021Article
- T Cell Protein Tyrosine Phosphatase in Glucose Metabolism.Frontiers in cell and developmental biology · 2021Review
- T Cell Protein Tyrosine Phosphatase in Osteoimmunology.Frontiers in immunology · 2021Review
- Multiplexable fluorescence lifetime imaging (FLIM) probes for Abl and Src-family kinases.Chemical communications (Cambridge, England) · 2020Article
- Modulation of TCR Signaling by Tyrosine Phosphatases: From Autoimmunity to Immunotherapy.Frontiers in cell and developmental biology · 2020Review
- Advances in Knowledge of Candidate Genes Acting at the Beta-Cell Level in the Pathogenesis of T1DM.Frontiers in endocrinology · 2020Review
17 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
The human protein tyrosine phosphatase TCPTP exists as two forms: an endoplasmic reticulum-targeted 48-kDa form (TC48) and a nuclear 45-kDa form (TC45). Although targeted to the nucleus, TC45 can exit in response to specific stimuli to dephosphorylate cytoplasmic substrates. In this study, we investigated the downregulation of insulin receptor (IR) signaling by TCPTP. In response to insulin stimulation, the TC48-D182A and TC45-D182A "substrate-trapping" mutants formed stable complexes with the endogenous tyrosine-phosphorylated IR beta-subunit in 293 cells. Moreover, in response to insulin stimulation, the TC45-D182A mutant accumulated in the cytoplasm of cells overexpressing the IR and in part colocalized with the IR beta-subunit at the cell periphery. These results indicate that the IR may serve as a cellular substrate for both TC48 and TC45. In immortalized TCPTP(-/-) murine embryo fibroblasts, insulin-induced IR beta-subunit tyrosine phosphorylation and protein kinase PKB/Akt activation were enhanced relative to the values in TCPTP(+/+) cells. Importantly, the expression of TC45 or TC48 to physiological levels suppressed the enhanced insulin-induced signaling in TCPTP(-/-) cells. These results indicate that the differentially localized variants of TCPTP may dephosphorylate the IR and downregulate insulin-induced signaling in vivo.
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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.