Affinage

PLAT

Tissue-type plasminogen activator · UniProt P00750

Round 2 corrected
Length
562 aa
Mass
62.9 kDa
Annotated
2026-04-28
71 papers in source corpus 20 papers cited in narrative 20 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PLAT encodes tissue-type plasminogen activator (tPA), a multi-domain serine protease that converts plasminogen to plasmin and thereby serves as a principal initiator of fibrinolysis, with additional non-proteolytic signaling roles in the nervous system, bone, and other tissues. The protein comprises a signal peptide, finger, EGF-like, two kringle, and serine protease domains encoded by 14 exons; the active-site serine (Ser-478) cleaves plasminogen, while surface-loop residues Arg-298/Arg-299 mediate rapid covalent inhibition by PAI-1, a serpin whose activity is enhanced by vitronectin, and the resulting tPA–PAI-1 complexes are cleared via LRP-mediated endocytosis (PMID:6337343, PMID:2110366, PMID:1695900, PMID:1502153). Beyond fibrinolysis, tPA acts non-proteolytically through its finger domain to activate microglia via annexin II binding, signals through LRP to enhance cAMP-PKA–dependent late-phase LTP in hippocampal neurons, and proteolytically cleaves IGFBP3 to liberate IGF1 and activate the IGF1R/PI3K-AKT-mTOR neuroprotective axis after ischemic stroke (PMID:11978811, PMID:10632583, PMID:34520334). tPA additionally functions downstream of Wnt1/β-Catenin in mechanically induced osteoblast differentiation and upstream of Erk1/2 in oocyte survival, and promotes FAK/AKT-dependent cancer cell invasion in drug-resistant lung adenocarcinoma (PMID:38407813, PMID:41252074, PMID:39754146).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1983 High

    Cloning and sequencing of tPA established it as a multi-domain serine protease that converts plasminogen to plasmin, resolving the molecular identity of the fibrinolytic activator.

    Evidence cDNA cloning, E. coli expression, and protein sequencing of the 527-amino-acid protein

    PMID:6337343

    Open questions at the time
    • Catalytic mechanism and active-site residue confirmation not yet performed
    • Gene structure and chromosomal location unknown
  2. 1984 High

    Biochemical characterization confirmed the active-site Ser-478 and mapped glycosylation sites, defining the post-translational landscape of mature tPA and explaining the two glycoform variants.

    Evidence Peptide mapping by RP-HPLC, Edman sequencing, DFP inactivation, and CNBr cleavage of purified tPA

    PMID:6433976

    Open questions at the time
    • Three-dimensional structure not yet determined
    • Functional role of individual glycosylation sites in activity or clearance unknown
  3. 1986 High

    Complete gene structure determination (14 exons, 36.6 kb, chromosome 8) revealed domain-exon correspondence consistent with exon shuffling, explaining how tPA acquired its modular architecture.

    Evidence Cosmid library screening, complete DNA sequencing, transcription start-site mapping, somatic cell hybrid chromosomal assignment

    PMID:3002960 PMID:3009482 PMID:6089198

    Open questions at the time
    • Promoter regulation and tissue-specific expression mechanisms not characterized
    • Functional significance of 28 intronic Alu repeats unknown
  4. 1986 High

    Identification and kinetic characterization of PAI-1 as a serpin that forms a rapid, covalent 1:1 complex with tPA established the principal physiological inhibitor of fibrinolysis.

    Evidence Plasma kinetic assays (~10⁷ M⁻¹s⁻¹), affinity purification from U-937 cells, SDS-PAGE complex analysis, partial amino acid sequencing

    PMID:20217999 PMID:3090045

    Open questions at the time
    • Structural basis of tPA–PAI-1 interaction at the residue level not yet defined
    • Role of cofactors in modulating PAI-1 inhibitory specificity not established
  5. 1990 High

    Mutagenesis pinpointed Arg-298/Arg-299 as the molecular determinants of PAI-1 recognition, and vitronectin was shown to act as a protein cofactor enhancing PAI-1's inhibition of tPA — together defining the two-layered specificity control of tPA inhibition.

    Evidence Site-directed mutagenesis with kinetic assays separating PAI-1 inhibition from plasminogen catalysis; reactive-center mutagenesis of PAI-1 with vitronectin cofactor kinetics

    PMID:1695900 PMID:2110366

    Open questions at the time
    • Crystal structure of the tPA–PAI-1–vitronectin ternary complex not available
    • In vivo significance of vitronectin cofactor effect on fibrinolytic balance not tested
  6. 1992 High

    Discovery that tPA–PAI-1 complexes are cleared via LRP-mediated endocytosis resolved how active tPA is removed from circulation and implicated LRP as a multifunctional tPA receptor.

    Evidence Solution binding, endocytosis/degradation assays in cultured cells, blocking with anti-LRP antibodies and RAP

    PMID:1502153

    Open questions at the time
    • LRP domain(s) responsible for tPA–PAI-1 binding not mapped
    • Hepatic vs. neuronal clearance contribution not distinguished
  7. 1993 High

    Identification of amphoterin (HMGB1) as a cell-surface cofactor that enhances tPA-mediated plasminogen activation at the leading edge of migrating cells extended tPA function beyond intravascular fibrinolysis to pericellular proteolysis during cell migration.

    Evidence In vitro plasminogen activation reconstitution with recombinant amphoterin, immunostaining of motile cells

    PMID:8366113

    Open questions at the time
    • Direct binding interface between tPA and HMGB1 not mapped
    • In vivo relevance to wound healing or metastasis not tested
  8. 2000 High

    Demonstration that tPA binding to neuronal LRP enhances cAMP-PKA signaling and is required for late-phase LTP established a non-fibrinolytic, receptor-mediated signaling role for tPA in synaptic plasticity.

    Evidence Hippocampal slice electrophysiology with RAP perfusion, tPA-knockout rescue, metabolic labeling, cAMP-PKA activity assays

    PMID:10632583

    Open questions at the time
    • Whether tPA signals through LRP as free protease or as tPA–PAI-1 complex in neurons not resolved
    • Downstream PKA substrates mediating L-LTP not identified
  9. 2002 High

    Mapping the microglial activation function to the finger domain of tPA and identifying annexin II as its receptor revealed a purely non-proteolytic cytokine-like mechanism, expanding tPA's functional repertoire beyond protease activity.

    Evidence Domain-deletion and catalytically inactive tPA constructs tested on microglial cultures, annexin II binding assays

    PMID:11978811

    Open questions at the time
    • Downstream signaling cascade in microglia triggered by finger-domain–annexin II interaction not defined
    • Relevance to in vivo neuroinflammation confirmed only indirectly
  10. 2021 High

    Identification of IGFBP3 as a tPA substrate whose cleavage liberates IGF1 to activate IGF1R/PI3K-AKT-mTOR and suppress autophagy provided a neuroprotective mechanism for tPA thrombolysis beyond clot lysis, validated in human stroke patients.

    Evidence In vitro hypoxia-reperfusion, in vivo thromboembolic stroke model, IGFBP3 cleavage assay, IGF1R inhibitor (picropodophyllin), human patient samples

    PMID:34520334

    Open questions at the time
    • IGFBP3 cleavage site on the substrate not mapped
    • Whether this neuroprotective pathway is engaged during endogenous tPA release (without pharmacological dosing) is unclear
  11. 2024 Medium

    Placing Plat downstream of Wnt1/β-Catenin in mechanically stimulated osteoblasts, with Plat knockdown blocking osteogenic marker induction, revealed an unexpected role for tPA in skeletal mechanotransduction and a potential link to osteoporosis.

    Evidence Mechanical stimulation of osteoblasts, siRNA knockdown of Wnt1 and Plat, RNAseq, OVX and aged mouse models

    PMID:38407813

    Open questions at the time
    • Mechanism by which tPA promotes osteogenesis (proteolytic vs. non-proteolytic) not determined
    • Findings from a single lab, awaiting independent replication
  12. 2025 Medium

    Emerging evidence places tPA upstream of Erk1/2 in oocyte survival and upstream of FAK/AKT in cancer cell invasion, broadening its signaling repertoire to reproductive biology and drug-resistant cancer.

    Evidence siRNA knockdown of Plat in oocytes with apoptosis/ferroptosis and Erk1/2 readouts; PLAT knockdown in gefitinib-resistant NSCLC with FAK/PI3K/AKT western blot and xenograft assays

    PMID:39754146 PMID:41252074

    Open questions at the time
    • Direct physical interaction between tPA and Alk or other kinases in oocytes awaits biochemical validation
    • Whether tPA's role in cancer invasion is proteolytic (plasmin-dependent) or receptor-mediated is unresolved
    • Both findings are from single laboratories

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis of tPA's non-proteolytic signaling through LRP and annexin II, the full repertoire of tPA substrates beyond plasminogen and IGFBP3, and whether the osteogenic and oocyte-survival functions are clinically relevant remain open questions.
  • No high-resolution structure of tPA in complex with LRP or annexin II
  • Systematic substrate profiling (degradomics) of tPA not performed
  • In vivo genetic validation of tPA roles in bone and oocyte biology lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 4 GO:0060089 molecular transducer activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005576 extracellular region 5 GO:0005886 plasma membrane 2
Pathway
R-HSA-109582 Hemostasis 5 R-HSA-162582 Signal Transduction 5 R-HSA-112316 Neuronal System 2 R-HSA-5357801 Programmed Cell Death 2

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1983 Human tissue-type plasminogen activator (tPA/PLAT) was cloned and expressed in E. coli; cDNA sequencing revealed a 527-amino-acid serine protease with a signal peptide, a heavy chain containing growth-factor-like and kringle domains, and a light chain comprising the serine protease catalytic domain, establishing tPA as a multi-domain serine protease that converts plasminogen to plasmin. cDNA cloning, expression in E. coli, protein sequencing Nature High 6337343
1984 Peptide analysis of purified tPA protein confirmed the cDNA-derived primary structure, identified Ser-478 as the active-site serine (inactivated by diisopropyl phosphorofluoridate), localized N-linked glycosylation to Asn-117, Asn-184 (the site distinguishing variant I from variant II by differential carbohydrate addition), and Asn-448, while Asn-218 is not glycosylated. Peptide mapping by reverse-phase HPLC, Edman sequencing, CNBr cleavage, DFP inactivation Biochemistry High 6433976
1984 The human PLAT gene spans >32 kb and is organized into 14 exons separated by 13 introns; exon-intron boundaries correspond closely to functional and structural protein domains (signal peptide, propeptide, finger/fibronectin-like, growth factor-like, two kringles each encoded by two exons, and the serine protease domain split by four introns in a pattern similar to other serine proteases), demonstrating exon shuffling in the evolution of tPA. Cosmid library screening, restriction mapping, Southern blotting, DNA sequencing Proceedings of the National Academy of Sciences of the United States of America High 6089198
1986 Complete nucleotide sequence of the PLAT gene (36,594 bp) was established, confirming 14 exons and 13 introns, identifying TATA and CAAT boxes upstream of the transcription start site, and revealing 28 Alu repeats within the gene; comparison with urokinase plasminogen activator indicated close evolutionary relationship between the two human plasminogen activators. Complete DNA sequencing, S1 nuclease, exonuclease VII, and primer extension mapping of transcription start site The Journal of biological chemistry High 3009482
1986 The human PLAT gene was mapped to chromosome 8 using rodent-human somatic cell hybrids probed with a 1.2-kb 3'-terminal cDNA fragment. Somatic cell hybrid panel, Southern blotting Human genetics High 3002960
1983 A rapid inhibitor of tPA (later identified as PAI-1) was demonstrated in plasma; kinetic analysis showed it forms a 1:1 complex with tPA with a second-order rate constant of ~10^7 M^-1 s^-1, indicating tight and rapid inhibitory control of tPA activity in blood. Plasma t-PA activity assay, kinetic analysis of inhibition Thrombosis research High 20217999
1986 PAI-1 purified from phorbol-ester-treated U-937 cells forms covalent (SDS-stable) complexes with two-chain tPA with a second-order rate constant of 0.2 × 10^6 M^-1 s^-1 and with urokinase at 0.9 × 10^6 M^-1 s^-1; partial amino acid sequencing identified PAI-1 as a member of the antithrombin III (serpin) family, establishing the serpin mechanism of tPA inhibition. Affinity chromatography purification, SDS-PAGE complex analysis, NH4OH cleavage, partial amino acid sequencing, inhibition kinetics The Journal of biological chemistry High 3090045
1990 Site-directed mutagenesis of the serine protease domain of tPA identified a surface loop (residues 296–302) whose positively charged residues Arg-298 and Arg-299 form ionic interactions with complementary negatively charged residues C-terminal to the reactive center of PAI-1; triple mutation (Lys296Glu/Arg298Glu/Arg299Glu) produced a tPA variant highly resistant to PAI-1 without affecting plasminogen catalysis, defining the molecular basis of tPA–PAI-1 specificity. Site-directed mutagenesis, kinetic analysis of PAI-1 inhibition, plasminogen activation assays Proceedings of the National Academy of Sciences of the United States of America High 2110366
1990 Vitronectin acts as a protein cofactor that dramatically enhances PAI-1 inhibition of tPA (and, when PAI-1 reactive center is mutated to match antithrombin III, of thrombin), establishing that a non-protein-cofactor mechanism can alter serpin specificity through protein–protein interaction and demonstrating that PAI-1 is a versatile inhibitor of fibrinolysis modulated by vitronectin. Reactive-center mutagenesis of PAI-1, kinetic inhibition assays ± vitronectin, SDS-PAGE complex analysis The Journal of biological chemistry High 1695900
1992 tPA-PAI-1 complexes bind in solution to the low-density lipoprotein receptor-related protein (LRP/α2-macroglobulin receptor) and are subsequently endocytosed and degraded in cultured cells; internalization was blocked by anti-LRP antibodies or the 39-kDa LRP-binding protein (RAP), identifying LRP as the clearance receptor for tPA-inhibitor complexes. Solution binding assays, endocytosis/degradation assays in cultured cells, antibody blocking, RAP inhibition Proceedings of the National Academy of Sciences of the United States of America High 1502153
1993 Amphoterin (HMGB1) strongly enhances the rate of plasminogen activation by tPA (tissue-type) and promotes generation of surface-bound plasmin; extracellular amphoterin is localized at the leading edge of motile cells and undergoes plasminogen-dependent degradation at cell-substrate contact sites, identifying amphoterin as a cell-surface co-factor that stimulates tPA-mediated plasmin generation at sites of cell migration. In vitro plasminogen activation assays with recombinant amphoterin, immunostaining, plasminogen-dependent degradation assay The Journal of biological chemistry High 8366113
1995 tPA mRNA expression was induced in cerebellar Purkinje neurons within one hour of complex motor task training; tPA protein was correspondingly upregulated in Purkinje cells, implicating tPA in activity-dependent synaptic remodeling and motor learning in the cerebellum. In situ hybridization, immunohistochemistry in motor-trained rats Science Medium 8533091
2000 tPA receptor LRP is abundantly expressed in hippocampal neurons; perfusion with the LRP antagonist RAP significantly reduced late-phase LTP (L-LTP), and RAP blocked tPA-enhanced synaptic potentiation in tPA-knockout hippocampal slices. Metabolic labeling confirmed both tPA and LRP are synthesized by hippocampal neurons; tPA binding to LRP enhances cAMP-dependent protein kinase activity, placing tPA–LRP interaction upstream of PKA in the L-LTP signaling cascade. Hippocampal slice electrophysiology, RAP perfusion, metabolic labeling, ligand binding assay, cAMP-PKA activity measurement The Journal of neuroscience High 10632583
2002 The finger domain of tPA (not its catalytic activity) is required to mediate microglial activation; annexin II was identified as the probable binding partner/receptor for the tPA finger domain at the microglial surface, indicating that tPA acts as a neural cytokine through a non-proteolytic mechanism to activate microglia during excitotoxic injury. Cell culture studies with tPA domain deletion/mutant constructs, identification of annexin II by binding assays, wild-type vs. catalytically inactive tPA comparison The Journal of neuroscience High 11978811
2004 Strong tetanic stimulation inducing L-LTP and training in hippocampal-dependent memory tasks enhance tPA expression and secretion; inhibition of tPA by gene knockout or specific inhibitors significantly impairs L-LTP and long-term memory, placing tPA as a required secreted factor downstream of strong synaptic activity for long-term memory consolidation. tPA knockout mouse behavioral and electrophysiology studies, pharmacological inhibition of tPA, biochemical analysis of tPA secretion Ageing research reviews Medium 15541709
2017 ADAM9 silencing in lung cancer cells suppressed PLAT (tPA) expression along with VEGFA and ANGPT2, leading to decreases in angiogenesis, vascular remodeling, and tumor growth in vivo, identifying PLAT as a downstream effector of ADAM9-driven vascular remodeling in brain metastasis. ADAM9 siRNA knockdown, microarray gene expression, in vivo tumor growth assay Scientific reports Low 29118335
2021 PLAT/tPA treatment following ischemia decreases deleterious autophagy and mediates neuroprotection by modulating the PI3K-AKT-mTOR pathway; mechanistically, tPA degrades IGFBP3, thereby increasing free IGF1 bioavailability and activating IGF1R (a tyrosine kinase receptor), which in turn activates PI3K-AKT-mTOR to suppress autophagy. This was demonstrated in hypoxia-reperfusion in vitro models, in vivo thromboembolic stroke with tPA thrombolysis, and corroborated in human stroke patients. In vitro hypoxia-reperfusion models, in vivo thromboembolic stroke model, IGFBP3 cleavage assay, PI3K-AKT-mTOR pathway analysis, IGF1R inhibitor (picropodophyllin), human patient samples Autophagy High 34520334
2024 Mechanical stimulation of osteoblasts induces Wnt1 expression, which activates β-Catenin, and β-Catenin in turn upregulates Plat expression; siRNA knockdown of Plat prevented mechanical stimulation-induced upregulation of osteogenic markers Runx2 and Sp7, placing Plat downstream of Wnt1/β-Catenin as a required mediator of mechanically induced osteoblast differentiation. Plat and Wnt1 expression were reduced in bones from ovariectomized and aged (osteoporotic) mice. Mechanical stimulation of osteoblasts, siRNA knockdown of Wnt1 and Plat, RNAseq, β-Catenin activation analysis, qPCR for osteogenic markers, OVX mouse model FASEB journal Medium 38407813
2025 In mouse oocytes, Plat (encoding tPA) is downregulated with aging; Plat knockdown increases oocyte susceptibility to both apoptosis and ferroptosis. Mechanistically, tPA acts as an upstream signaling molecule that activates the Erk1/2 pathway by interacting with phosphorylation kinases including Alk; Plat loss reduces Erk1/2 activity, leading to oocyte degeneration through programmed cell death. Supplementation with exogenous tPA in in vitro maturation cultures reduced defect rates in aged oocytes. Transcriptomic analysis of single oocytes, siRNA knockdown of Plat, apoptosis/ferroptosis pathway inhibitors, Erk1/2 phosphorylation assay, exogenous tPA supplementation in IVM cultures Science China. Life sciences Medium 41252074
2025 In gefitinib-resistant NSCLC cells, PLAT knockdown reduced migration and invasion by downregulating TNC, ITGB3, and the phosphorylation of FAK, PI3K, and AKT, placing PLAT upstream of the FAK/AKT signaling pathway that drives cell motility and invasion in drug-resistant lung adenocarcinoma. Whole-transcriptome sequencing, siRNA/lentiviral knockdown of PLAT, cell migration/invasion assays, western blot for p-FAK, p-PI3K, p-AKT, in vivo NSG mouse xenograft Chinese medicine Medium 39754146

Source papers

Stage 0 corpus · 71 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2020 A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature 3411 32353859
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2000 Plat-E: an efficient and stable system for transient packaging of retroviruses. Gene therapy 1437 10871756
1983 Cloning and expression of human tissue-type plasminogen activator cDNA in E. coli. Nature 1155 6337343
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2004 The PDGF family: four gene products form five dimeric isoforms. Cytokine & growth factor reviews 618 15207811
2020 Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms. Science (New York, N.Y.) 564 33060197
1983 Evidence for a rapid inhibitor to tissue plasminogen activator in plasma. Thrombosis research 510 20217999
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
1989 SPARC, a secreted protein associated with cellular proliferation, inhibits cell spreading in vitro and exhibits Ca+2-dependent binding to the extracellular matrix. The Journal of cell biology 356 2745554
1984 The structure of the human tissue-type plasminogen activator gene: correlation of intron and exon structures to functional and structural domains. Proceedings of the National Academy of Sciences of the United States of America 304 6089198
1995 Tissue plasminogen activator induction in Purkinje neurons after cerebellar motor learning. Science (New York, N.Y.) 267 8533091
2004 Regulation of late-phase LTP and long-term memory in normal and aging hippocampus: role of secreted proteins tPA and BDNF. Ageing research reviews 255 15541709
1992 Complexes of tissue-type plasminogen activator and its serpin inhibitor plasminogen-activator inhibitor type 1 are internalized by means of the low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor. Proceedings of the National Academy of Sciences of the United States of America 248 1502153
2000 Role of tissue plasminogen activator receptor LRP in hippocampal long-term potentiation. The Journal of neuroscience : the official journal of the Society for Neuroscience 235 10632583
1986 Purification and characterization of a plasminogen activator inhibitor from the histiocytic lymphoma cell line U-937. The Journal of biological chemistry 233 3090045
2010 MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis. Immunology and cell biology 221 20458337
1992 The PLAT Study: hemostatic function in relation to atherothrombotic ischemic events in vascular disease patients. Principal results. PLAT Study Group. Progetto Lombardo Atero-Trombosi (PLAT) Study Group. Arteriosclerosis and thrombosis : a journal of vascular biology 204 1525121
1990 Isolation of human fos-related genes and their expression during monocyte-macrophage differentiation. Oncogene 192 2107490
1993 Amphoterin, the 30-kDa protein in a family of HMG1-type polypeptides. Enhanced expression in transformed cells, leading edge localization, and interactions with plasminogen activation. The Journal of biological chemistry 179 8366113
1986 The human tissue plasminogen activator gene. The Journal of biological chemistry 176 3009482
2002 Tissue plasminogen activator mediates microglial activation via its finger domain through annexin II. The Journal of neuroscience : the official journal of the Society for Neuroscience 175 11978811
1990 Alteration of serpin specificity by a protein cofactor. Vitronectin endows plasminogen activator inhibitor 1 with thrombin inhibitory properties. The Journal of biological chemistry 165 1695900
2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip. American journal of human genetics 164 19913121
2004 An unappreciated role for RNA surveillance. Genome biology 159 14759258
1984 Tissue plasminogen activator: peptide analyses confirm an indirectly derived amino acid sequence, identify the active site serine residue, establish glycosylation sites, and localize variant differences. Biochemistry 153 6433976
1990 Amino acid residues that affect interaction of tissue-type plasminogen activator with plasminogen activator inhibitor 1. Proceedings of the National Academy of Sciences of the United States of America 150 2110366
1993 FGFRI and PLAT genes and DNA amplification at 8p12 in breast and ovarian cancers. Genes, chromosomes & cancer 149 7692948
2000 Short tandem-repeat polymorphism/alu haplotype variation at the PLAT locus: implications for modern human origins. American journal of human genetics 67 10986042
1991 The PLAT Study: a multidisciplinary study of hemostatic function and conventional risk factors in vascular disease patients. Atherosclerosis 53 1759983
2004 ATP-2 interacts with the PLAT domain of LOV-1 and is involved in Caenorhabditis elegans polycystin signaling. Molecular biology of the cell 48 15563610
2014 The Arabidopsis PLAT domain protein1 is critically involved in abiotic stress tolerance. PloS one 46 25396746
2017 ADAM9 promotes lung cancer progression through vascular remodeling by VEGFA, ANGPT2, and PLAT. Scientific reports 44 29118335
2014 Reduced expression of TLR3, TLR10 and TREM1 by human macrophages in Chronic cavitary pulmonary aspergillosis, and novel associations of VEGFA, DENND1B and PLAT. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases 33 24712925
1991 Recurrent homogeneously staining regions in 8p1 in breast cancer and lack of amplification of POLB, LHRH, and PLAT genes. Cancer genetics and cytogenetics 29 1706959
2019 Nodule-specific PLAT domain proteins are expanded in the Medicago lineage and required for nodulation. The New phytologist 27 30664233
2021 Thrombolysis by PLAT/tPA increases serum free IGF1 leading to a decrease of deleterious autophagy following brain ischemia. Autophagy 24 34520334
2019 The Nodule-Specific PLAT Domain Protein NPD1 Is Required for Nitrogen-Fixing Symbiosis. Plant physiology 21 31061106
1986 Assignment of the human tissue-type plasminogen activator gene (PLAT) to chromosome 8. Human genetics 20 3002960
2018 DNA Methylation of Proximal PLAT Promoter in Chronic Rhinosinusitis With Nasal Polyps. American journal of rhinology & allergy 17 29962211
2011 Positive association of phencyclidine-responsive genes, PDE4A and PLAT, with schizophrenia. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 16 21898905
2020 Knockdown of PLAT enhances the anticancer effect of gefitinib in non-small cell lung cancer. Journal of thoracic disease 13 32274137
2019 A Select and Resequence Approach Reveals Strain-Specific Effects of Medicago Nodule-Specific PLAT-Domain Genes. Plant physiology 12 31653715
2015 The Arabidopsis PLAT domain protein1 promotes abiotic stress tolerance and growth in tobacco. Transgenic research 11 25757741
2014 Effect of hypoxia on the expression of CCN2, PLAU, PLAUR, SLURP1, PLAT and ITGB1 genes in ERN1 knockdown U87 glioma cells. Ukrainian biochemical journal 8 25509186
1991 Dinucleotide repeat polymorphism at the human tissue plasminogen activator gene (PLAT). Nucleic acids research 8 1945894
2025 Outcomes of PLAT-02 and PLAT-03: evaluating CD19 CAR T-cell therapy and CD19-expressing T-APC support in pediatric B-ALL. Blood 7 40233328
2024 Mechanical induction of osteoanabolic Wnt1 promotes osteoblast differentiation via Plat. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 7 38407813
2023 PLAT domain protein 1 (PLAT1/PLAFP) binds to the Arabidopsis thaliana plasma membrane and inserts a lipid. Plant science : an international journal of experimental plant biology 7 37863269
2013 Structural representative of the protein family PF14466 has a new fold and establishes links with the C2 and PLAT domains from the widely distant Pfams PF00168 and PF01477. Protein science : a publication of the Protein Society 5 23681886
2025 Aidi injection inhibits the migration and invasion of gefitinib-resistant lung adenocarcinoma cells by regulating the PLAT/FAK/AKT pathway. Chinese medicine 4 39754146
2025 Single-cell multi-omics reveals that FABP1 + renal cell carcinoma drive tumor angiogenesis through the PLG-PLAT axis under fatty acid reprogramming. Molecular cancer 4 40518526
2018 [MicroRNA in Body Fluids - Development of the Novel Plat Form for Cancer Therapeutics and Diagnosis]. Gan to kagaku ryoho. Cancer & chemotherapy 3 30026410
2016 [Role of PLAT, PKHD1L1, STK38L and TEAD1 genes Alu-polymorphism for longevity]. Advances in gerontology = Uspekhi gerontologii 2 28556638
2000 Immune system activation by CDDP and "poly-plat". Anticancer research 2 10953351
2025 Mutation in soybean Lox-2 PLAT/LH2 domain through CRISPR/Cas9 reduces seed lipoxygenase activity: responsible for undesirable flavour. Transgenic research 1 40498336
2025 High-fat diets influence breast cancer progression by modulating CAF-immune cell interactions through PLAT signaling. The Journal of pathology 1 40899255
2021 Rapid prototyping of PDMS microdevices viaµPLAT on nonplanar surfaces with flexible hollow-out mask. Biofabrication 1 33418543
2015 Backbone assignment and secondary structure of the PLAT domain of human polycystin-1. Biomolecular NMR assignments 1 25943267
2007 Population genetic data on four STR loci, PAI (CA)n, GpIIIa (CT)n, PLAT (TG)14 (CA)12, and NOS2A (CCTTT)n, in Mediterranean populations. Legal medicine (Tokyo, Japan) 1 17320454
1997 Paraganglioma-Like Adenomas of the Thyroid (PLAT): Incidental Lesions with Unusual Features in a Patient with Nodular Goiter. Endocrine pathology 1 12114635
2026 Analysis of ATF6 and PLAT Expressions in Relation to hsa-miR-340-5p in Childhood Obesity. International journal of molecular sciences 0 41898467
2025 Plat safeguards maternally aged oocytes against programmed cell death through activating the Erk1/2 pathway. Science China. Life sciences 0 41252074
2002 Mechanisms of actio of poly-plat, a novel platinum antineoplastic agent. Anticancer research 0 12174899
2002 An improved assay for genotyping the common Alu insertion in the tissue-type plasminogen activation gene PLAT. Genetic testing 0 12180080
1993 [The fabrication technique of Plat casting ceramic prosthesis: A preliminary study]. Shanghai kou qiang yi xue = Shanghai journal of stomatology 0 15159853