Receptor-type tyrosine-protein phosphatase beta · UniProt P23467
PTPRB (VE-PTP) is a receptor-type protein tyrosine phosphatase that acts as a negative regulator of receptor tyrosine kinase signaling in vascular and epithelial contexts, with its phosphatase catalytic activity required for these functions (PMID:30845793). It directly restrains TEK/TIE2 receptor kinase signaling: genetic reduction of Ptprb in Tek-haploinsufficient mice elevated TEK phosphorylation, restored Schlemm's canal development, and prevented ocular hypertension and retinal ganglion cell loss (PMID:31621585). PTPRB likewise dephosphorylates VEGFR2 to suppress brown adipocyte differentiation—an effect abolished by an active-site mutant (PMID:30845793)—and limits FGFR/ERK1/2 activation to constrain mammary branching morphogenesis (PMID:28870991). In tumor settings PTPRB modulates Src phosphorylation and invasion in NSCLC (PMID:27314562) and acts upstream of TWIST1-dependent EMT in colorectal cancer (PMID:31040266). Consistent with a tumor-suppressive role, recurrent truncating loss-of-function mutations occur in angiosarcoma (PMID:24633157). Its phosphatase activity is amplified by physical interaction with exosomal SPRY4, which enhances TIE2 dephosphorylation and dampens downstream PI3K/AKT signaling (PMID:40660390).
Established the chromosomal location of human PTPRB, providing the genomic anchor for later disease-association studies.
Evidence In situ hybridization with a cDNA probe mapping to 12q15→q21
Identified PTPRB as a recurrent loss-of-function driver in angiosarcoma, framing it as a negative regulator of vascular growth-factor tyrosine kinases.
Evidence Whole-genome, whole-exome, and targeted sequencing of angiosarcoma tumors revealing truncating mutations in 26%
Positioned PTPRB upstream of Src in lung cancer, linking its phosphatase function to invasion control.
Evidence shRNA knockdown/overexpression with phospho-Src Western blotting and pharmacological rescue by PP2, plus xenograft
Demonstrated PTPRB restrains FGFR/ERK signaling to limit epithelial branching, extending its RTK-negative-regulator role to morphogenesis.
Evidence In vivo shRNA knockdown in mammary fat pad transplants and organoids with phospho-FGFR and phospho-ERK1/2 readouts
Connected PTPRB to Hippo-pathway control as a miRNA-suppressed effector in hepatocellular carcinoma.
Evidence Luciferase reporter validation of miR-665 targeting plus functional rescue in cell and in vivo assays
Showed PTPRB phosphatase activity directly inactivates VEGFR2 to block brown adipogenesis, providing catalytic-dependence evidence via active-site mutagenesis.
Evidence Overexpression of wild-type vs catalytic-dead PTPRB with phospho-VEGFR2 Western blot and adipocyte marker analysis
Provided clean in vivo genetic proof that PTPRB directly antagonizes TEK/TIE2 signaling in Schlemm's canal development and IOP control.
Evidence Tek+/-;Ptprb+/- double-haploinsufficiency mice with IOP, canal morphology, RGC counts, and TEK phosphorylation readouts
Placed PTPRB upstream of TWIST1-dependent EMT and as a Hippo-linked miRNA target across additional cancers, broadening its tumor-modulating role.
Evidence Epistasis with TWIST1 knockdown in colorectal cells and luciferase/rescue in osteosarcoma with miR-624-5p, plus in vivo models
Linked PTPRB signal-peptide integrity to cardiac development through a Mendelian variant.
Evidence Whole-genome sequencing and minigene splicing assay of a homozygous splice-acceptor variant in a single family with hypoplastic left heart syndrome
Identified a direct physical regulator of PTPRB, showing SPRY4 binding enhances its phosphatase activity against TIE2 and dampens PI3K/AKT-driven angiogenesis.
Evidence Reciprocal Co-IP with mass spectrometry, phospho-TIE2 and PI3K/AKT Western blots, tube formation assays, and an in vivo rat SONFH model
| Year | Finding | Method | Journal | Conf | PMIDs |
|---|---|---|---|---|---|
| 2014 | PTPRB harbors predominantly truncating (loss-of-function) somatic mutations in 26% of angiosarcomas (10/39 tumors), identifying it as a negative regulator of vascular growth factor tyrosine kinases and a recurrent driver in angiosarcoma. | Whole-genome, whole-exome, and targeted sequencing of primary and secondary angiosarcoma tumors | Nature genetics | Medium | 24633157 |
| 2019 | Deletion of a single allele of Ptprb in Tek haploinsufficient mice elevated TEK phosphorylation, restored Schlemm's canal development, and prevented ocular hypertension and retinal ganglion cell loss, establishing PTPRB as a direct negative regulator of TEK (Tie2) receptor kinase signaling in the aqueous humor outflow pathway. | Genetic epistasis in mice (Tek+/-;Ptprb+/- double haploinsufficiency), measurement of IOP, Schlemm's canal morphology, and RGC counts | eLife | High | 31621585 |
| 2018 | PTPRB is a direct downstream target of miR-665 in hepatocellular carcinoma; its restoration reverses miR-665-driven migration, invasion, and proliferation, and PTPRB mediates these effects through regulation of the Hippo signaling pathway. | Luciferase reporter assay (direct target validation), Western blotting, gain/loss-of-function cell assays, in vitro and in vivo functional rescue experiments | Cell death & disease | Medium | 30237408 |
| 2019 | PTPRB is a direct downstream target of miR-624-5p in osteosarcoma; PTPRB restoration reverses miR-624-5p-driven migration and invasion, with the Hippo signaling pathway identified as the downstream effector of the miR-624-5p/PTPRB axis. | Luciferase reporter assay, Western blotting, gain/loss-of-function cell and mouse tumorigenicity assays | Journal of experimental & clinical cancer research | Medium | 31829261 |
| 2016 | PTPRB regulates Src phosphorylation in NSCLC cells; knockdown of PTPRB increased Src phosphorylation and cell invasion, effects reversed by the Src inhibitor PP2, placing PTPRB as a phosphatase upstream of Src in lung cancer signaling. | Lentiviral overexpression/shRNA knockdown, phospho-Src Western blotting, pharmacological rescue with PP2, xenograft mouse model | Clinical and experimental pharmacology & physiology | Medium | 27314562 |
| 2017 | PTPRB negatively regulates branching morphogenesis in the mouse mammary epithelium by modulating FGFR signaling; Ptprb knockdown increased FGFR activation and ERK1/2 phosphorylation at baseline and after FGF2 stimulation, resulting in increased branching density in vivo and in organoids. | In vivo shRNA knockdown in cleared mammary fat pad transplants, in vitro organoid assay, phospho-FGFR and phospho-ERK1/2 Western blotting | Development | Medium | 28870991 |
| 2019 | PTPRB promotes epithelial-mesenchymal transition (EMT) and metastasis in colorectal cancer cells; PTPRB overexpression decreased vimentin and increased E-cadherin expression; hypoxia-induced EMT and invasion were eliminated by PTPRB knockdown; TWIST1 knockdown blocked migration even when PTPRB was overexpressed, placing PTPRB upstream of TWIST1-dependent EMT. | shRNA knockdown and cDNA overexpression, wound-healing and invasion assays, in vivo metastasis model, Western blotting for EMT markers, epistasis with TWIST1 knockdown | Cell death & disease | Medium | 31040266 |
| 2019 | PTPRB inhibits brown adipocyte differentiation through its phosphatase activity; ectopic PTPRB overexpression suppressed tyrosine phosphorylation of VEGFR2 and downregulated brown adipocyte genes (UCP-1, PGC-1α, PRDM16, PPARγ, CIDEA), while a catalytically inactive PTPRB mutant had no effect on differentiation or VEGFR2 phosphorylation. | Overexpression of wild-type vs. catalytic-dead PTPRB mutant, phospho-VEGFR2 Western blotting, gene expression analysis of brown adipocyte markers | Journal of microbiology and biotechnology | Medium | 30845793 |
| 1992 | The human PTPRB gene was localized to chromosome 12q15→q21 by in situ hybridization using a cDNA probe. | In situ hybridization with cDNA probe | Cytogenetics and cell genetics | Medium | 1486802 |
| 2022 | A rare homozygous splice-acceptor variant in PTPRB (c.56-2A>C) causes aberrant mRNA splicing with deletion of one amino acid (p.Glu19del) in the signal peptide of VE-PTP, associated with hypoplastic left heart syndrome, implicating PTPRB signal peptide integrity in cardiac development. | Whole-genome sequencing, Sanger confirmation, minigene splicing assay, in silico structure prediction | Clinical genetics | Low | 36148623 |
| 2025 | Exosomal SPRY4 from adipogenic BMSCs directly interacts with PTPRB and enhances its phosphatase activity, causing inhibition of TIE2 receptor autophosphorylation and suppression of downstream PI3K/AKT signaling, thereby impairing angiogenesis in steroid-induced osteonecrosis of the femoral head. | Co-immunoprecipitation and mass spectrometry (SPRY4-PTPRB interaction), Western blotting (TIE2 phosphorylation, PI3K/AKT), tube formation and migration assays, in vivo rat SONFH model with pharmacological modulation | Stem cell research & therapy | Medium | 40660390 |
| 2024 | Forsythoside A ameliorates pulmonary fibrosis partly via PTPRB; pharmacological inhibition of PTPRB attenuated the effect of forsythoside A on TGF-β1-induced endothelial-to-mesenchymal transition (EndMT) in HUVECs and fibroblast proliferation in HFL1 cells, placing PTPRB as a required mediator of the anti-fibrotic response. | Pharmacological inhibition of PTPRB in TGF-β1-stimulated HUVECs and HFL1 cells, Western blotting for EMT/fibrosis markers, mouse BLM model | Phytomedicine | Low | 38788399 |
| Year | Title | Journal | Citations | PMID |
|---|---|---|---|---|
| 2014 | Recurrent PTPRB and PLCG1 mutations in angiosarcoma. | Nature genetics | 258 | 24633157 |
| 2017 | Graphene/Intermetallic PtPb Nanoplates Composites for Boosting Electrochemical Detection of H2O2 Released from Cells. | Analytical chemistry | 99 | 28206749 |
| 2018 | miR-665 promotes hepatocellular carcinoma cell migration, invasion, and proliferation by decreasing Hippo signaling through targeting PTPRB. | Cell death & disease | 82 | 30237408 |
| 2007 | Structural basis for selective inhibition of Mycobacterium tuberculosis protein tyrosine phosphatase PtpB. | Structure (London, England : 1993) | 82 | 17437721 |
| 2017 | PtPb/PtNi Intermetallic Core/Atomic Layer Shell Octahedra for Efficient Oxygen Reduction Electrocatalysis. | Journal of the American Chemical Society | 73 | 28657302 |
| 2008 | Pt-Pb nanowire array electrode for enzyme-free glucose detection. | Biosensors & bioelectronics | 68 | 18619831 |
| 2011 | Synthesis, biological evaluation, and molecular modeling of chalcone derivatives as potent inhibitors of Mycobacterium tuberculosis protein tyrosine phosphatases (PtpA and PtpB). | Journal of medicinal chemistry | 62 | 22136336 |
| 2005 | Mycobacterium tuberculosis protein tyrosine phosphatase PtpB structure reveals a diverged fold and a buried active site. | Structure (London, England : 1993) | 60 | 16271885 |
| 2013 | Discovery of Mycobacterium tuberculosis protein tyrosine phosphatase B (PtpB) inhibitors from natural products. | PloS one | 55 | 24155919 |
| 2019 | miR-624-5p promoted tumorigenesis and metastasis by suppressing hippo signaling through targeting PTPRB in osteosarcoma cells. | Journal of experimental & clinical cancer research : CR | 44 | 31829261 |
| 2017 | Defects and Interfaces on PtPb Nanoplates Boost Fuel Cell Electrocatalysis. | Small (Weinheim an der Bergstrasse, Germany) | 43 | 29165911 |
| 2019 | Targeting the vascular-specific phosphatase PTPRB protects against retinal ganglion cell loss in a pre-clinical model of glaucoma. | eLife | 29 | 31621585 |
| 2020 | PSMD11, PTPRM and PTPRB as novel biomarkers of pancreatic cancer progression. | Biochimica et biophysica acta. General subjects | 24 | 32663515 |
| 2010 | Dynamic active-site protection by the M. tuberculosis protein tyrosine phosphatase PtpB lid domain. | Journal of the American Chemical Society | 24 | 20230004 |
| 2005 | Interaction of PTPB with the insulin receptor precursor during its biosynthesis in the endoplasmic reticulum. | Biochimie | 24 | 15733745 |
| 2023 | Sub-Monolayer SbO on PtPb/Pt Nanoplate Boosts Direct Formic Acid Oxidation Catalysis. | Journal of the American Chemical Society | 20 | 37585588 |
| 2019 | PTPRB promotes metastasis of colorectal carcinoma via inducing epithelial-mesenchymal transition. | Cell death & disease | 17 | 31040266 |
| 2016 | Protein tyrosine phosphatase PTPRB regulates Src phosphorylation and tumour progression in NSCLC. | Clinical and experimental pharmacology & physiology | 17 | 27314562 |
| 2019 | Dual-targeting GroEL/ES chaperonin and protein tyrosine phosphatase B (PtpB) inhibitors: A polypharmacology strategy for treating Mycobacterium tuberculosis infections. | Bioorganic & medicinal chemistry letters | 16 | 31047750 |
| 2017 | The receptor protein tyrosine phosphatase PTPRB negatively regulates FGF2-dependent branching morphogenesis. | Development (Cambridge, England) | 16 | 28870991 |
| 2010 | Design and synthesis of nonpeptidic, small molecule inhibitors for the Mycobacterium tuberculosis protein tyrosine phosphatase PtpB. | Organic & biomolecular chemistry | 16 | 20644889 |
| 2008 | Association of PTPRB gene polymorphism with drug addiction. | American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics | 14 | 18361428 |
| 2024 | Forsythoside A regulates pulmonary fibrosis by inhibiting endothelial-to-mesenchymal transition and lung fibroblast proliferation via the PTPRB signaling. | Phytomedicine : international journal of phytotherapy and phytopharmacology | 13 | 38788399 |
| 2008 | Electrocatalytic mechanism and kinetics of SOMs oxidation on ordered PtPb and PtBi intermetallic compounds: DEMS and FTIRS study. | Physical chemistry chemical physics : PCCP | 13 | 18563235 |
| 2011 | Electrodeposition of chitosan-glucose oxidase biocomposite onto Pt-Pb nanoparticles modified stainless steel needle electrode for amperometric glucose biosensor. | Journal of materials science. Materials in medicine | 11 | 21671000 |
| 2025 | Rare genetic variation in PTPRB is associated with central serous chorioretinopathy, varicose veins and glaucoma. | Nature communications | 10 | 40319023 |
| 2019 | Protein Tyrosine Phosphatase, Receptor Type B (PTPRB) Inhibits Brown Adipocyte Differentiation through Regulation of VEGFR2 Phosphorylation. | Journal of microbiology and biotechnology | 9 | 30845793 |
| 1992 | The gene for receptor-like protein tyrosine phosphatase (PTPRB) is assigned to chromosome 12q15-->q21. | Cytogenetics and cell genetics | 8 | 1486802 |
| 2022 | Novel rare mutation in a conserved site of PTPRB causes human hypoplastic left heart syndrome. | Clinical genetics | 7 | 36148623 |
| 2025 | Exosomal SPRY4 from adipogenic BMSCs impairs angiogenesis via the PTPRB/TIE2/PI3K axis in Steroid-induced osteonecrosis of the femoral head. | Stem cell research & therapy | 6 | 40660390 |
| 2009 | Analyzing the catalytic mechanism of protein tyrosine phosphatase PtpB from Staphylococcus aureus through site-directed mutagenesis. | International journal of biological macromolecules | 5 | 19747503 |
| 2021 | The Low-Molecular Weight Protein Arginine Phosphatase PtpB Affects Nuclease Production, Cell Wall Integrity, and Uptake Rates of Staphylococcus aureus by Polymorphonuclear Leukocytes. | International journal of molecular sciences | 4 | 34069497 |
| 2010 | Fabrication and surface characterization of single crystal PtBi and PtPb (100) and (001) surfaces. | Physical chemistry chemical physics : PCCP | 4 | 20820559 |
| 2025 | Solvothermal synthesis of PtPb nanoparticles with efficient alcohol oxidation performance. | Nanoscale | 2 | 40927927 |
| 2022 | The variants in PTPRB, TRAF3IP3, and DISC1 genes were associated with Graves' disease in the Chinese population. | Medicine | 1 | 36397361 |
| 2025 | Mycobacterial Tyrosine Phosphatase PtpB Affects Host Cytokine Expression by Dephosphorylating ERK1/2 and STAT3. | Molecular & cellular proteomics : MCP | 0 | 40935154 |
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