Affinage

TPO

Thyroid peroxidase · UniProt P07202

Length
933 aa
Mass
103.0 kDa
Annotated
2026-04-28
100 papers in source corpus 24 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

The gene symbol TPO maps to two distinct genes: thrombopoietin (THPO) and thyroid peroxidase (TPO). Thrombopoietin is the primary cytokine regulating megakaryopoiesis and platelet production; it binds the c-Mpl receptor to activate JAK2, which phosphorylates STAT3/STAT5 and recruits Gab1/2–PI3K–Akt and Ras–MAPK cascades, with the adaptor Lnk acting as a negative regulator through its SH2 domain, and circulating TPO levels are homeostatically controlled by platelet mass via c-Mpl-mediated uptake (PMID:7544303, PMID:9474742, PMID:15337790, PMID:11402314). The relative expression levels of JAK2 and MPL determine whether TPO signaling drives megakaryocyte proliferation or differentiation, and TPO additionally promotes hematopoietic stem cell self-renewal through p38 MAPK–USF-1–Hoxb4 induction (PMID:25143485, PMID:12855555). Thyroid peroxidase is a heme-containing enzyme essential for thyroid hormone biosynthesis that catalyzes iodide organification independently of NIS; its cryo-EM structure reveals a four-domain monomer with catalytic histidines His239 and His494, and loss-of-function mutations causing residual activity below ~15% result in severe congenital hypothyroidism (PMID:36537574, PMID:15062578, PMID:32088313).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1995 High

    Identification of JAK2–STAT5/STAT3 and Ras pathway activation downstream of TPO/c-Mpl established the core signaling framework through which thrombopoietin controls megakaryocyte biology.

    Evidence Immunoprecipitation and phosphorylation assays in hematopoietic cell lines showing TPO-induced phosphorylation of JAK2, STAT5, STAT3, Shc, Sos, Vav, and c-Cbl

    PMID:7488109 PMID:7544303

    Open questions at the time
    • Relative contribution of each downstream pathway to proliferation vs. differentiation was not resolved
    • Identity of direct JAK2 substrates on c-Mpl cytoplasmic tail not mapped
  2. 1998 High

    TPO and c-mpl knockout mice demonstrated that TPO is the dominant non-redundant regulator of megakaryopoiesis and platelet production, and that circulating TPO is homeostatically regulated by platelet mass through receptor-mediated uptake.

    Evidence Genetic knockout mice showing 90% platelet reduction, reduced progenitors, decreased megakaryocyte ploidy, and inverse relationship between platelet mass and TPO levels

    PMID:9474742

    Open questions at the time
    • Relative contributions of hepatic production vs. other tissue sources of TPO not fully dissected
    • Whether residual 10% platelet production depends on alternative cytokines was unclear
  3. 1998 Low

    Sequence-based analysis of thyroid peroxidase identified the catalytic proximal (His494) and distal (His239) histidines and predicted why the TPO-2 splice variant lacking Asn579 is enzymatically inactive.

    Evidence Sequence alignment of TPO with myeloperoxidase and multi-species peroxidases, comparative analysis of TPO vs. TPO-2 splice variant

    PMID:9510129

    Open questions at the time
    • No direct mutagenesis was performed in this study to validate the histidine assignments
    • Structural basis remained computational inference without experimental structure
  4. 2001 High

    Mapping of Gab1/2 recruitment to c-Mpl phospho-Y112 and its requirement for PI3K/Akt activation resolved how TPO couples to the pro-proliferative PI3K pathway through a specific receptor tyrosine.

    Evidence Co-immunoprecipitation and Y112 site-directed mutagenesis in UT7 and Ba/F3 cells with PI3K activity and proliferation assays

    PMID:11402314

    Open questions at the time
    • Whether other receptor tyrosines contribute to PI3K activation was not excluded
    • Structural basis for Gab1/2 recognition of pY112 not determined
  5. 2003 Medium

    TPO was linked to hematopoietic stem cell self-renewal through p38 MAPK–USF-1–Hoxb4 induction, extending TPO function beyond megakaryopoiesis to multipotent progenitor maintenance.

    Evidence Gene expression analysis in EML and UT-7/TPO cells, tpo−/− mouse comparison, p38 inhibition and USF-1 induction assays

    PMID:12855555

    Open questions at the time
    • Whether Hoxb4 induction is the sole mediator of TPO-driven HSC expansion was untested
    • Single laboratory finding
  6. 2003 Medium

    Thyroid peroxidase was confirmed as the obligate catalyst for iodide organification, functioning independently of the sodium-iodide symporter NIS.

    Evidence Stable transfection of TPO and NIS constructs with 125I organification assays and specific inhibitors in thyroid cancer cells

    PMID:15062578

    Open questions at the time
    • Only tested in cancer cell line context, not primary thyrocytes
    • Coupling between NIS-mediated iodide transport and TPO at the apical membrane not mechanistically resolved
  7. 2004 High

    Identification of Lnk as a negative regulator of TPO/c-Mpl signaling, acting through its SH2 domain to attenuate STAT3, STAT5, Akt, and MAPK pathways, revealed a key feedback control node in megakaryopoiesis.

    Evidence Lnk overexpression and knockout mice, western blot, megakaryocyte culture, domain mutagenesis

    PMID:15337790

    Open questions at the time
    • Direct binding partner of Lnk SH2 domain on c-Mpl or JAK2 not mapped
    • Lnk regulation of other cytokine receptors not distinguished from TPO-specific effects
  8. 2006 Medium

    Dissection of PI3K–Akt–mTOR versus MEK–ERK pathways showed that mTOR is required for TPO-induced polyploidization while MEK opposes it, clarifying how a single cytokine directs both proliferation and endomitotic differentiation.

    Evidence Pharmacological inhibition (rapamycin, PD98059) in CD34+ cell-derived megakaryocyte cultures with ploidy analysis

    PMID:16449323

    Open questions at the time
    • Pharmacological inhibitors lack complete specificity
    • Direct mTOR substrates mediating polyploidization not identified
  9. 2007 High

    NMR structural characterization of the c-Mpl transmembrane and juxtamembrane region in complex with a small-molecule agonist revealed a two-helix architecture and identified His-499 as a critical contact, providing a structural basis for non-peptide TPO mimetics.

    Evidence Solution and solid-state NMR, domain swap and site-directed mutagenesis of c-Mpl

    PMID:17369254

    Open questions at the time
    • Full-length receptor structure with native TPO ligand not determined
    • Whether the small-molecule activation mechanism fully mimics TPO-induced conformational change was unclear
  10. 2014 Medium

    Demonstration that JAK2 and MPL expression levels gate the proliferation-versus-differentiation decision resolved the paradox of how graded TPO signaling generates distinct megakaryocyte fates.

    Evidence shRNA knockdown of JAK2/MPL, JAK2 chemical inhibitors in UT7-MPL cells, patient sample analysis, in vivo mouse studies

    PMID:25143485

    Open questions at the time
    • Quantitative thresholds for the switch not precisely defined
    • Whether this applies to HSC compartment or only committed megakaryocyte progenitors unclear
  11. 2020 Medium

    Genotype-phenotype correlation for thyroid peroxidase missense mutations established that residual enzymatic activity below ~15% causes severe congenital hypothyroidism, directly linking TPO catalytic function to disease severity.

    Evidence In vitro TPO enzyme activity assays of mutant constructs correlated with clinical phenotypes in 230 Chinese congenital hypothyroidism patients

    PMID:32088313

    Open questions at the time
    • Activity measurements in vitro may not fully reflect in vivo folding and trafficking
    • Cohort from single ethnic background
  12. 2023 High

    Cryo-EM structures of human thyroid peroxidase resolved its four-domain architecture, heme environment, and autoantibody epitope locations, providing the first near-atomic model of this enzyme.

    Evidence Cryo-EM of purified hTPO–Fab complexes at 3.4–3.92 Å resolution

    PMID:36537574

    Open questions at the time
    • Structure of TPO in complex with thyroglobulin substrate not determined
    • Catalytic mechanism of iodination not captured at atomic detail in transition-state analogs

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis for TPO (thrombopoietin) binding to full-length c-Mpl and the conformational changes that discriminate proliferative from differentiative signaling remain unresolved; for thyroid peroxidase, the mechanism of substrate (thyroglobulin) recognition and coupling reaction at the apical membrane has not been structurally characterized.
  • No full-length TPO–c-Mpl complex structure exists
  • Structural basis for thyroglobulin coupling by thyroid peroxidase is unknown
  • How TPO signaling strength is quantitatively decoded into distinct transcriptional programs is mechanistically unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 5 GO:0048018 receptor ligand activity 4 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 3 GO:0005576 extracellular region 2
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-1266738 Developmental Biology 3 R-HSA-1430728 Metabolism 3 R-HSA-109582 Hemostasis 2 R-HSA-168256 Immune System 2
Partners
GAB1GAB2JAK2LNKMPLSTAT3STAT5TNS2

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 TPO (thrombopoietin) binding to c-Mpl induces tyrosine phosphorylation and activation of STAT5 and STAT3, defining a rapid JAK-STAT signaling pathway downstream of the TPO receptor. Immunoprecipitation, electrophoretic mobility shift assay (EMSA), tyrosine phosphorylation assays in hematopoietic cell lines FEBS letters High 7544303
1995 TPO/c-mpl signaling induces tyrosine phosphorylation of JAK2, Shc, Sos (Ras pathway components), Vav, and c-Cbl, indicating activation of both JAK/STAT and Ras signaling pathways downstream of c-Mpl. Tyrosine phosphorylation assays and immunoprecipitation in Mo7e megakaryoblastic cells Biochemical and biophysical research communications High 7488109
1998 TPO knockout and c-mpl knockout mice show 90% reduction in platelets due to reduced hematopoietic progenitor numbers and decreased megakaryocyte ploidy; circulating TPO levels are regulated by platelet mass through c-Mpl-mediated binding and uptake, establishing a feedback mechanism for TPO homeostasis. Genetic knockout mouse models, bone marrow analysis, platelet counts, repopulation assays Stem cells (Dayton, Ohio) High 9474742
2004 The adaptor protein Lnk negatively regulates TPO/c-Mpl signaling; Lnk overexpression attenuates TPO-induced STAT3, STAT5, Akt, and MAPK activation, and Lnk deficiency results in enhanced megakaryocyte numbers and ploidy. The SH2 domain of Lnk is essential for its inhibitory function. Lnk overexpression and knockout mouse studies, western blot for signaling pathway activation, megakaryocyte culture assays, domain mutagenesis The Journal of experimental medicine High 15337790
2001 Upon TPO stimulation, adaptor proteins Gab1 and Gab2 are tyrosine phosphorylated and associate with Shc, SHP2, PI3-kinase, and Grb2; Gab proteins are the principal PI3-kinase-associated proteins after TPO stimulation. Tyrosine residue Y112 in the C-terminal cytoplasmic domain of c-Mpl is required for Gab1/2 phosphorylation and subsequent PI3-kinase/Akt pathway activation, which is required for TPO-induced cell proliferation. Co-immunoprecipitation, c-Mpl Y112 mutant expression in UT7 cells and Ba/F3 cells, PI3-kinase activity assays, proliferation assays Oncogene High 11402314
2003 TPO stimulates Hoxb4 expression via p38 MAPK, which induces the transcription factor USF-1; this molecular pathway provides a mechanism by which TPO promotes hematopoietic stem cell self-renewal and expansion. Gene expression analysis in EML and UT-7/TPO cells, tpo-/- mouse comparison, p38 inhibition studies, USF-1 induction assays Blood Medium 12855555
2006 TPO-induced megakaryocyte polyploidization requires the PI3K-AKT-mTOR-p70S6K pathway; inhibition of MEK increases ploidy while inhibition of mTOR strongly inhibits polyploidization. Cyclin D3 nuclear localization correlates with MEK inhibition-induced polyploidy. Pharmacological inhibition (PD98059 for MEK, rapamycin for mTOR) in CD34+ cell-derived megakaryocyte cultures, western blot for pathway activation, DNA content analysis Journal of cell science Medium 16449323
2007 A small nonpeptidyl TPO receptor agonist (SB394725) interacts specifically with His-499 in the transmembrane domain and residues in the extracellular juxtamembrane region (JMR) of c-Mpl; the JMR-TM region consists of two alpha-helices separated by non-helical residues, revealing a distinct mechanism of cytokine receptor activation by small molecules. NMR structural studies (solution and solid-state), receptor domain swap, site-directed mutagenesis The Journal of biological chemistry High 17369254
2011 Tensin2 interacts with c-Mpl at phospho-Tyrosine631 and becomes phosphorylated in a TPO-dependent manner; knockdown of Tensin2 dramatically reduces TPO-dependent cell proliferation and Akt signaling, identifying Tensin2 as a novel mediator in the TPO/c-Mpl pathway. Peptide microarray (SH2/PTB domains), co-precipitation with pY631 peptide, siRNA knockdown, proliferation and Akt phosphorylation assays Cell cycle (Georgetown, Tex.) Medium 21527831
2014 JAK2 and MPL protein expression levels determine whether TPO signaling drives megakaryocyte proliferation or differentiation; decreased JAK2 or MPL expression or JAK2 inhibition suppresses the antiproliferative action of TPO, and low-dose JAK2 inhibitors paradoxically increase megakaryocyte production in vitro and in vivo. shRNA knockdown of JAK2/MPL in UT7-MPL cells, JAK2 chemical inhibitors, analysis of patient samples, in vivo mouse studies Blood Medium 25143485
1998 TPO stimulation of TF-1/TPO cells induces tyrosine phosphorylation of the common beta subunit (βc) of GM-CSF/IL-3 receptor and its association with Stat5 (but not Shc), demonstrating cross-talk between c-Mpl and GM-CSF/IL-3 receptor signaling pathways. Immunoprecipitation, western blot for tyrosine phosphorylation, co-precipitation of Stat5 and Shc in TF-1/TPO cells Biochemical and biophysical research communications Medium 9600081
2000 Platelets store and release biologically active full-length TPO upon activation with platelet agonists; platelet fractionation indicates TPO is contained in granules. In vivo, platelet activation in DIC patients correlates with elevated plasma TPO, suggesting platelets function as a releasable storage pool for TPO. Platelet activation assays, platelet fractionation, ELISA for TPO in patient samples Thrombosis and haemostasis Medium 10896250
1996 TPO activates JAK2 tyrosine kinase and STAT5-related protein tyrosine phosphorylation in the UT-7/TPO megakaryocytic cell line, and drives megakaryocytic maturation including increased ploidy and platelet factor-4 expression. Western blot for JAK2 and STAT5 tyrosine phosphorylation, RT-PCR for lineage markers in UT-7/TPO cells Blood Medium 8639823
2023 Cryo-EM structures of human TPO (thyroid peroxidase) show it as a monomer with four domains (N-terminal, peroxidase domain, CCP-like domain, EGF-like domain); a disulfide bond between Cys146 (POD) and Cys756 (CCP) fixes domain positions. The haem group, active site entrance, and calcium binding site are visible on the opposite side from autoantibody binding epitopes on the POD domain. Cryo-electron microscopy of purified hTPO in complex with Fab antibodies at 3.4–3.92 Å resolution Journal of molecular endocrinology High 36537574
1998 The proximal histidine (His494) and distal histidine (His239) of thyroid peroxidase (TPO) are essential for catalytic activity; Asn579 in the alternatively spliced region likely forms a stabilizing hydrogen bond with the proximal histidine, explaining the lack of enzymatic activity of the TPO-2 splice variant. Arg396 is conserved across peroxidases and likely participates in compound I formation. Amino acid sequence alignment with myeloperoxidase, comparative analysis of TPO vs TPO-2 splice variant, multi-species peroxidase alignment Thyroid Low 9510129
2018 Triclosan activates the p38 MAPK pathway in thyroid cells, which induces TRHr expression; this p38/TRHr axis then suppresses TPO (thyroid peroxidase) expression and activity, contributing to hypothyroidism. Rat in vivo triclosan exposure, cell treatment with p38 inhibitors and TRHr siRNA, western blot, RT-PCR in Nthy-ori 3-1 cells Cellular physiology and biochemistry Medium 29462796
2020 TPO (thrombopoietin) and its receptor c-Mpl are expressed in human CNS neurons; TPO exerts neuroprotective effects in hypoxic-ischemic neonatal rat brain models by promoting cell proliferation via PI3K/Akt signaling and inhibiting apoptosis via the Bcl-2/BAX pathway. Immunostaining of human CNS tissue, neonatal rat HI brain model, C17.2 cell proliferation assays, western blot for PI3K/Akt and Bcl-2/BAX pathway components Aging Medium 32341206
2013 IL-17A requires functional TPO/c-MPL signaling to exert its effects on granulopoiesis and megakaryopoiesis; in c-mpl-/- mice, IL-17A fails to expand megakaryocytes in bone marrow and does not cause peripheral neutrophil expansion, establishing TPO/c-mpl as required for IL-17A-induced hematopoietic effects. Genetic epistasis using c-mpl-/- mice with in vivo IL-17A expression, bone marrow and spleen colony-forming assays, cytokine measurements Journal of leukocyte biology Medium 23990627
2003 Raf-1 is dispensable for TPO-induced ERK1/2 phosphorylation in megakaryocytes and is not required for megakaryocytopoiesis; raf-1-/- megakaryocytes show normal TPO-induced ERK1/2 activation without compensatory upregulation of A-Raf or B-Raf, indicating other Raf family members mediate ERK activation downstream of TPO. raf-1-/- knockout mouse megakaryocyte analysis, TPO stimulation assays, western blot for ERK phosphorylation and Raf isoforms, ploidy analysis Blood High 14576068
2020 In vitro enzyme activity assays of TPO (thyroid peroxidase) missense mutations show that residual TPO enzymatic activity correlates with clinical severity: patients with <15% residual activity show severe congenital hypothyroidism, while those with >16% show mild phenotypes. In vitro TPO enzyme activity assays of mutant constructs, genotype-phenotype correlation in 230 Chinese CH patients Molecular and cellular endocrinology Medium 32088313
2003 Iodination of proteins by thyroid peroxidase (TPO) in thyroid cancer cells is strictly dependent on TPO enzymatic activity and independent of NIS (sodium-iodide symporter) function; co-expression of TPO and NIS shows organification requires TPO but not iodide uptake via NIS. Stable transfection of TPO and NIS constructs, 125I organification assays, specific inhibitors of TPO and NIS Molecular and cellular endocrinology Medium 15062578
2017 Lnk deficiency leads to increased TPO signaling and increased osteoclastogenesis; Lnk is expressed in osteoclast lineage cells and Lnk-/- osteoclast progenitors cultured with TPO produce significantly more osteoclasts than WT, establishing a direct role of TPO/c-Mpl/Lnk signaling in bone remodeling. Lnk-/- mouse bone phenotype analysis (microCT, histomorphometry), in vitro osteoclast differentiation with TPO, alkaline phosphatase assays in osteoblasts Journal of cellular biochemistry Medium 28067429
2018 TPO (thyroid peroxidase) expressed in breast tissue has enzymatic activity and isoelectric point comparable to thyroid TPO, but with decreased glycosylation and slightly lower molecular weight. In mammary cell lines, TPO is mainly cytoplasmic with insufficient cell-surface expression to detect enzymatic activity, and no dimer formation occurs. Western blot, enzymatic activity assays, isoelectric focusing, immunohistochemistry, panel of TPO-specific antibodies in breast tissue and cell lines PloS one Medium 29513734
2015 During megakaryocytic differentiation of UT-7/TPO cells, TPO induces upregulation of PDGFR-α and PDGFR-β and promotes formation of PDGFRαβ heterodimer complexes and complexes between PDGFRs and neuropilin-1 (NRP-1), suggesting NRP-1 participates in megakaryopoiesis through PDGFR interactions. Co-immunoprecipitation, western blot, immunocytochemistry in UT-7/TPO cells stimulated with TPO and PMA Biochemical and biophysical research communications Low 25744030

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2018 Repotrectinib (TPX-0005) Is a Next-Generation ROS1/TRK/ALK Inhibitor That Potently Inhibits ROS1/TRK/ALK Solvent- Front Mutations. Cancer discovery 398 30093503
2004 Lnk inhibits Tpo-mpl signaling and Tpo-mediated megakaryocytopoiesis. The Journal of experimental medicine 160 15337790
1996 Establishment and characterization of the thrombopoietin-dependent megakaryocytic cell line, UT-7/TPO. Blood 99 8639823
1999 Purification and characterization of a second type thioredoxin peroxidase (type II TPx) from Saccharomyces cerevisiae. Biochemistry 97 9888818
1998 Hematopoietic deficiencies in c-mpl and TPO knockout mice. Stem cells (Dayton, Ohio) 90 9474742
2010 Genetics and phenomics of hypothyroidism and goiter due to TPO mutations. Molecular and cellular endocrinology 88 20153806
1995 Production of thrombopoietin (TPO) by rat hepatocytes and hepatoma cell lines. Experimental hematology 86 7498368
2003 Thrombopoietin stimulates Hoxb4 expression: an explanation for the favorable effects of TPO on hematopoietic stem cells. Blood 83 12855555
2021 Thrombopoietin Receptor Agonists (TPO-RAs): Drug Class Considerations for Pharmacists. Drugs 79 34160821
1995 Thrombopoietin (TPO) induces tyrosine phosphorylation and activation of STAT5 and STAT3. FEBS letters 77 7544303
2021 TPX-0131, a Potent CNS-penetrant, Next-generation Inhibitor of Wild-type ALK and ALK-resistant Mutations. Molecular cancer therapeutics 75 34158340
2008 The Campylobacter jejuni thiol peroxidases Tpx and Bcp both contribute to aerotolerance and peroxide-mediated stress resistance but have distinct substrate specificities. Journal of bacteriology 70 18515414
2001 Tpx-1 is a component of the outer dense fibers and acrosome of rat spermatozoa. Molecular reproduction and development 69 11144214
2019 Causal Relationship Between Anti-TPO IgE and Chronic Urticaria by In Vitro and In Vivo Tests. Allergy, asthma & immunology research 68 30479075
2000 Platelets release thrombopoietin (Tpo) upon activation: another regulatory loop in thrombocytopoiesis? Thrombosis and haemostasis 66 10896250
2005 Relation of anti-TPO autoantibody titre and T-lymphocyte cytokine production patterns in Hashimoto's thyroiditis. Clinical endocrinology 65 16060913
1998 Molecular cloning of the rat Tpx-1 responsible for the interaction between spermatogenic and Sertoli cells. Biochemical and biophysical research communications 62 9675100
2017 Iodide handling disorders (NIS, TPO, TG, IYD). Best practice & research. Clinical endocrinology & metabolism 61 28648508
2013 Thrombopoietin levels in patients with disorders of platelet production: diagnostic potential and utility in predicting response to TPO receptor agonists. American journal of hematology 61 23913253
1995 TPO/c-mpl ligand induces tyrosine phosphorylation of multiple cellular proteins including proto-oncogene products, Vav and c-Cbl, and Ras signaling molecules. Biochemical and biophysical research communications 60 7488109
2007 NMR structural studies of interactions of a small, nonpeptidyl Tpo mimic with the thrombopoietin receptor extracellular juxtamembrane and transmembrane domains. The Journal of biological chemistry 55 17369254
2006 Inhibition of TPO-induced MEK or mTOR activity induces opposite effects on the ploidy of human differentiating megakaryocytes. Journal of cell science 55 16449323
1995 Genetic and epitopic analysis of thyroid peroxidase (TPO) autoantibodies: markers of the human thyroid autoimmune response. Clinical and experimental immunology 53 7544244
2020 TPO antibody positivity and adverse pregnancy outcomes. Best practice & research. Clinical endocrinology & metabolism 52 32883611
2014 JAK2 and MPL protein levels determine TPO-induced megakaryocyte proliferation vs differentiation. Blood 50 25143485
2013 Thyroid dyshormonogenesis is mainly caused by TPO mutations in consanguineous community. Clinical endocrinology 50 23236987
2014 Increased TRAb and/or low anti-TPO titers at diagnosis of graves' disease are associated with an increased risk of developing ophthalmopathy after onset. Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association 45 24554511
2019 Thrombopoietin receptor agonist (TPO-RA) treatment raises platelet counts and reduces anti-platelet antibody levels in mice with immune thrombocytopenia (ITP). Platelets 44 31146647
2021 Will the clinical development of 4th-generation "double mutant active" ALK TKIs (TPX-0131 and NVL-655) change the future treatment paradigm of ALK+ NSCLC? Translational oncology 43 34365220
2009 Acute and persistent Mycobacterium tuberculosis infections depend on the thiol peroxidase TpX. PloS one 42 19340292
2001 Role of Gab proteins in phosphatidylinositol 3-kinase activation by thrombopoietin (Tpo). Oncogene 39 11402314
2006 Goitrous congenital hypothyroidism and hearing impairment associated with mutations in the TPO and SLC26A4/PDS genes. The Journal of clinical endocrinology and metabolism 38 16684826
1999 A novel mutation in the TPO gene in goitrous hypothyroid patients with iodide organification defect. Clinical endocrinology 38 10468986
1998 Endogenous TPO (eTPO) levels in health and disease: possible clues for therapeutic intervention. Stem cells (Dayton, Ohio) 37 11012188
2008 TPO-independent megakaryocytopoiesis. Critical reviews in oncology/hematology 36 18093840
1994 Cloning and characterisation of TPO autoantibodies using combinatorial phage display libraries. Autoimmunity 36 7524700
2023 Prolonged response after TPO-RA discontinuation in primary ITP: results of a prospective multicenter study. Blood 34 36893453
2012 Immune function genes CD99L2, JARID2 and TPO show association with autism spectrum disorder. Molecular autism 34 22681640
2023 Ameliorative effects of mangiferin derivative TPX on insulin resistance via PI3K/AKT and AMPK signaling pathways in human HepG2 and HL-7702 hepatocytes. Phytomedicine : international journal of phytotherapy and phytopharmacology 33 36965373
2018 P38/TRHr-Dependent Regulation of TPO in Thyroid Cells Contributes to the Hypothyroidism of Triclosan-Treated Rats. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 32 29462796
2011 Octa-arginine mediated delivery of wild-type Lnk protein inhibits TPO-induced M-MOK megakaryoblastic leukemic cell growth by promoting apoptosis. PloS one 32 21853157
1991 Genetic linkage studies of thyroid peroxidase (TPO) gene in families with TPO deficiency. The Journal of clinical endocrinology and metabolism 32 1671388
2011 Molecular screening of the TSH receptor (TSHR) and thyroid peroxidase (TPO) genes in Korean patients with nonsyndromic congenital hypothyroidism. Clinical endocrinology 30 21707688
2017 Safety, Pharmacokinetics and Pharmacodynamics of Hetrombopag Olamine, a Novel TPO-R Agonist, in Healthy Individuals. Basic & clinical pharmacology & toxicology 29 28544774
2016 Identification of CHEK1, SLC26A4, c-KIT, TPO and TG as new biomarkers for human follicular thyroid carcinoma. Oncotarget 29 27329729
2006 Expression of TPO and ThOXs in human thyrocytes is downregulated by IL-1alpha/IFN-gamma, an effect partially mediated by nitric oxide. American journal of physiology. Endocrinology and metabolism 29 16478776
2011 A TPO receptor agonist, ALXN4100TPO, mitigates radiation-induced lethality and stimulates hematopoiesis in CD2F1 mice. Radiation research 28 21476857
2006 2-Cys Peroxiredoxin TPx-1 is involved in gametocyte development in Plasmodium berghei. Molecular and biochemical parasitology 27 16597467
2007 Clinical and genetic characteristics of congenital hypothyroidism due to mutations in the thyroid peroxidase (TPO) gene in Israelis. Clinical endocrinology 26 17381485
2000 Evidence for antigen presentation to sensitized T cells by thyroid peroxidase (TPO)-specific B cells in mice injected with fibroblasts co-expressing TPO and MHC class II. Clinical and experimental immunology 26 10606962
1999 Cellular thyroid peroxidase (TPO), unlike purified TPO and adjuvant, induces antibodies in mice that resemble autoantibodies in human autoimmune thyroid disease. The Journal of clinical endocrinology and metabolism 26 10323395
1995 Localization of TDPX1, a human homologue of the yeast thioredoxin-dependent peroxide reductase gene (TPX), to chromosome 13q12. Genomics 25 7607688
2011 Tensin2 is a novel mediator in thrombopoietin (TPO)-induced cellular proliferation by promoting Akt signaling. Cell cycle (Georgetown, Tex.) 24 21527831
2020 Increased Prevalence of TG and TPO Mutations in Sudanese Children With Congenital Hypothyroidism. The Journal of clinical endocrinology and metabolism 23 31867598
2020 Effects of butylparaben exposure on thyroid peroxidase (TPO) and type 1 iodothyronine deiodinase (D1) in female Wistar rats. Toxicology 23 32798586
2005 Mesenchymal stem cells support expansion of in vitro irradiated CD34(+) cells in the presence of SCF, FLT3 ligand, TPO and IL3: potential application to autologous cell therapy in accidentally irradiated victims. Radiation research 23 15966759
2000 Effects of flt-3 ligand in combination with TPO on the expansion of megakaryocytic progenitors. Cell transplantation 23 10784074
2020 Thyroid peroxidase in human endometrium and placenta: a potential target for anti-TPO antibodies. Clinical and experimental medicine 22 32980989
2013 The TPO/c-MPL pathway in the bone marrow may protect leukemia cells from chemotherapy in AML Patients. Pathology oncology research : POR 22 24085601
2019 Repotrectinib (TPX-0005), effectively reduces growth of ALK driven neuroblastoma cells. Scientific reports 21 31852910
2017 Genetically engineered mesenchymal stromal cells produce IL-3 and TPO to further improve human scaffold-based xenograft models. Experimental hematology 21 28456746
2015 Significance of CK19, TPO, and HBME-1 expression for diagnosis of papillary thyroid carcinoma. International journal of clinical and experimental medicine 21 26064355
2007 Optimal ex vivo expansion of neutrophils from PBSC CD34+ cells by a combination of SCF, Flt3-L and G-CSF and its inhibition by further addition of TPO. Journal of translational medicine 21 17971220
2003 Raf-1 is not required for megakaryocytopoiesis or TPO-induced ERK phosphorylation. Blood 21 14576068
2020 The TPO mutation screening and genotype-phenotype analysis in 230 Chinese patients with congenital hypothyroidism. Molecular and cellular endocrinology 20 32088313
2017 Cytokine changes in response to TPO receptor agonist treatment in primary immune thrombocytopenia. Cytokine 20 28142109
2016 Mutation screening of the TPO gene in a cohort of 192 Chinese patients with congenital hypothyroidism. BMJ open 20 27173810
2013 TPO genetic variants and risk of differentiated thyroid carcinoma in two European populations. International journal of cancer 20 23754668
2018 Biochemical properties of thyroid peroxidase (TPO) expressed in human breast and mammary-derived cell lines. PloS one 18 29513734
2017 Thyroid peroxidase (TPO) expressed in thyroid and breast tissues shows similar antigenic properties. PloS one 18 28575127
2017 Novel TPO receptor agonist TA-316 contributes to platelet biogenesis from human iPS cells. Blood advances 18 29296963
2014 Genetic analysis of thyroid peroxidase (TPO) gene in patients whose hypothyroidism was found in adulthood in West Bengal, India. Endocrine journal 18 24420335
2005 Human recombinant TSH preceding a therapeutic dose of radioiodine for multinodular goiters has no significant effect in the surge of TSH-receptor and TPO antibodies. Thyroid : official journal of the American Thyroid Association 17 15753672
2000 Thrombopoietin and the TPO receptorduring platelet storage. Transfusion 17 10960526
1999 Expression of ICAM-1, B7.1 and TPO on human thyrocytes induced by IFN-alpha. Chinese medical journal 17 11593644
1998 Thrombopoietin induces tyrosine phosphorylation of a common beta subunit of GM-CSF receptor and its association with Stat5 in TF-1/TPO cells. Biochemical and biophysical research communications 16 9600081
2022 The return of RET GateKeeper mutations? an in-silico exploratory analysis of potential resistance mechanisms to novel RET macrocyclic inhibitor TPX-0046. Investigational new drugs 15 35612671
2018 GLI1 Inhibitors Identified by Target Protein Oriented Natural Products Isolation (TPO-NAPI) with Hedgehog Inhibition. ACS chemical biology 15 30160475
2017 Developmental Stage-Specific Manifestations of Absent TPO/c-MPL Signalling in Newborn Mice. Thrombosis and haemostasis 14 29212120
2016 TPO-RAs in pITP: description of a case series and analysis of predictive factors for response. European journal of haematology 14 27797414
2016 Gender-dependent and age-of-onset-specific association of the rs11675434 single-nucleotide polymorphism near TPO with susceptibility to Graves' ophthalmopathy. Journal of human genetics 14 27829681
2013 Is there a link between Hashimoto's thyroiditis and primary hyperparathyroidism? A study of serum parathormone and anti-TPO antibodies in 2267 patients. Hellenic journal of nuclear medicine 14 23865082
2006 Congenital primary hypothyroidism with subsequent adenomatous goiter in a Turkish patient caused by a homozygous 10-bp deletion in the thyroid peroxidase (TPO) gene. Clinical endocrinology 14 16649969
1998 Thrombopoietin (TPO) knockout phenotype induced by cross-reactive antibodies against TPO following injection of mice with recombinant adenovirus encoding human TPO. Journal of immunology (Baltimore, Md. : 1950) 14 9574554
2020 Mild TPO deficiency characterized by progressive goiter and normal serum TSH level. Endocrine 13 32078117
2020 A Novel Thioredoxin-Dependent Peroxiredoxin (TPx-Q) Plays an Important Role in Defense Against Oxidative Stress and Is a Possible Drug Target in Babesia microti. Frontiers in veterinary science 13 32133382
2020 c-Mpl and TPO expression in the human central nervous system neurons inhibits neuronal apoptosis. Aging 13 32341206
2019 ASSOCIATION OF FOXP3 GENE VARIANTS WITH RISK OF HASHIMOTO'S THYROIDITIS AND CORRELATION WITH ANTI-TPO ANTIBODY LEVELS. Acta endocrinologica (Bucharest, Romania : 2005) 13 32377237
1998 Proximal and distal histidines in thyroid peroxidase: relation to the alternatively spliced form, TPO-2. Thyroid : official journal of the American Thyroid Association 13 9510129
1998 Proliferative reaction of myelogenous leukemia cells with cytokines G-CSF, GM-CSF, M-CSF, SCF and TPO. Leukemia research 13 9678722
2020 Homology between TSH-R/Tg/TPO and Hashimoto's encephalopathy autoantigens. Frontiers in bioscience (Landmark edition) 12 31585887
2014 One Base Deletion (c.2422delT) in the TPO Gene Causes Severe Congenital Hypothyroidism. Journal of clinical research in pediatric endocrinology 12 25241611
2003 Iodination of proteins in TPO transfected thyroid cancer cells is independent of NIS. Molecular and cellular endocrinology 12 15062578
2023 Cryo-electron microscopy structures of human thyroid peroxidase (TPO) in complex with TPO antibodies. Journal of molecular endocrinology 11 36537574
2023 TPO as an indicator of lymph node metastasis and recurrence in papillary thyroid carcinoma. Scientific reports 11 37407700
2023 The association of Treg and Th17 cells development factors and anti-TPO autoantibodies in patients with recurrent pregnancy loss. BMC research notes 11 37907956
2017 Lnk Deficiency Leads to TPO-Mediated Osteoclastogenesis and Increased Bone Mass Phenotype. Journal of cellular biochemistry 11 28067429
2015 Platelet-derived growth factor receptors form complexes with neuropilin-1 during megakaryocytic differentiation of thrombopoietin-dependent UT-7/TPO cells. Biochemical and biophysical research communications 11 25744030
2013 Requirement of TPO/c-mpl for IL-17A-induced granulopoiesis and megakaryopoiesis. Journal of leukocyte biology 11 23990627
2012 Fibronectin promotes proplatelet formation in the human megakaryocytic cell line UT-7/TPO. Cell biology international 11 21970435