Affinage

SLC20A1

Sodium-dependent phosphate transporter 1 · UniProt Q8WUM9

Length
679 aa
Mass
73.7 kDa
Annotated
2026-04-28
100 papers in source corpus 20 papers cited in narrative 20 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SLC20A1 (PiT1) is a sodium-dependent inorganic phosphate cotransporter with a 12-transmembrane-helix topology that serves dual roles as a gammaretrovirus receptor and a signaling scaffold with transport-independent functions in cell proliferation, apoptosis, ER homeostasis, and inflammation (PMID:19717569, PMID:19726692, PMID:20817733, PMID:30347511, PMID:30755642). As a phosphate transporter, PiT1 mediates Pi uptake that drives osteogenic transdifferentiation and vascular calcification in smooth muscle cells and is rate-limiting for bone mineralization in osteoblasts (PMID:16527991, PMID:17438129). Independent of its transport activity, PiT1 forms Pi-regulated heterodimers with PiT2 that activate ERK1/2 signaling to sense extracellular phosphate, sustains cell proliferation via p38 MAPK suppression, protects against TNF-induced apoptosis by limiting JNK/caspase-8 activation, and participates in a positive feedback loop with NF-κB in macrophage inflammatory responses (PMID:29233890, PMID:19726692, PMID:20817733, PMID:30755642). Complete PiT1 deletion in mice causes embryonic lethality at E12.5 with liver hypoplasia, anemia, and yolk sac vascular defects, while hematopoietic-specific loss impairs EKLF-driven erythroid maturation, underscoring essential, non-redundant developmental roles (PMID:20161774, PMID:23190530).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1993 High

    Identifying the molecular determinants of retroviral receptor function established that a small region (residues 550–551, region A/loop 4) of SLC20A1 controls species-specific GALV entry, providing the first structure–function map of the protein.

    Evidence Chimeric human/mouse GLVR1 constructs and point mutagenesis with GALV infection readout

    PMID:8411375

    Open questions at the time
    • Direct virus–receptor binding contacts not mapped
    • Whether region A also affects phosphate transport was not tested
  2. 1998 High

    Demonstrating that SLC20A1 functions as a Na⁺-dependent Pi cotransporter in heterologous expression, and that a single amino acid insertion in region A can broaden retroviral receptor specificity, established the protein's dual transport/receptor identity and the structural plasticity of the receptor-determining loop.

    Evidence Xenopus oocyte Pi transport assay; gain-of-function mutagenesis conferring A-MuLV susceptibility; dietary Pi/vitamin D regulation in rat parathyroid

    PMID:9343161 PMID:9528951 PMID:9557753

    Open questions at the time
    • Stoichiometry and kinetics of Na⁺:Pi coupling not resolved
    • Whether region A mutations affect transport kinetics unknown
  3. 2002 High

    Resolving that a second extracellular region (residues 232–260, region B) is required for actual GALV/FeLV-B virus binding — while region A mutations affect membrane topology rather than direct binding — reframed the structural basis for receptor function.

    Evidence Epitope-tagged PiT1 topology analysis, direct virus binding assays, compensatory mutagenesis

    PMID:12097582

    Open questions at the time
    • No crystal or cryo-EM structure of PiT1 available
    • Whether Pi binding and virus binding are competitive was not tested
  4. 2006 High

    Showing that PiT1-mediated Pi uptake is required for vascular smooth muscle cell osteogenic transdifferentiation and calcification, and that BMP-2 selectively induces PiT1 via JNK to drive mineralization, placed PiT1 as a central effector linking extracellular phosphate to pathological vascular and physiological bone mineralization.

    Evidence siRNA knockdown and retroviral overexpression in human SMCs with calcification and osteogenic marker readouts; antisense PiT1 and JNK inhibitor in osteoblast-like cells

    PMID:16527991 PMID:16734382

    Open questions at the time
    • Whether intracellular Pi itself or a downstream metabolite triggers osteogenic gene induction unclear
    • In vivo confirmation in conditional VSMC-specific knockout not yet done
  5. 2007 High

    Bidirectional manipulation of PiT1 in osteoblasts and local in vivo foscarnet injection demonstrated that PiT1-dependent Pi transport is rate-limiting for bone mineralization, extending its mineralization role from pathological (vascular) to physiological (skeletal) contexts.

    Evidence Pit1 over/underexpression in osteoblast cultures; calvarial foscarnet injection in vivo

    PMID:17438129

    Open questions at the time
    • Foscarnet is not specific to PiT1 — it inhibits NaPi transport generally
    • Downstream Pi-sensing mechanism in osteoblasts not identified
  6. 2009 High

    Discovery that non-transporting PiT1 mutants fully rescue cell proliferation defects and that PiT1 depletion activates p38 MAPK revealed the first transport-independent signaling function, fundamentally expanding PiT1's role beyond a transporter.

    Evidence RNAi in HeLa/HepG2, rescue with transport-dead mutants, xenograft tumors, MAPK phosphorylation

    PMID:19726692

    Open questions at the time
    • Direct binding partner mediating p38 MAPK regulation unknown
    • Whether the proliferation role is cell-type-universal not tested
  7. 2009 High

    SCAM analysis in live cells resolved PiT1 as a 12-transmembrane-helix protein with 7 extracellular regions, correcting prior 10-TM models and providing the structural framework for interpreting both transport and receptor functions.

    Evidence Substituted cysteine accessibility mutagenesis with glycosylation mapping

    PMID:19717569

    Open questions at the time
    • No high-resolution 3D structure
    • Pi binding site not mapped at atomic resolution
  8. 2010 High

    PiT1 knockout mice dying at E12.5 with liver hypoplasia and anemia, and transport-dead PiT1 rescuing TNF-induced apoptosis sensitivity, established that PiT1 is essential in vivo and that its anti-apoptotic role (via JNK/caspase-8 suppression) is transport-independent.

    Evidence Null and conditional allele mice with developmental phenotyping; siRNA/KO MEFs with TNF stimulation and rescue with transport-dead mutant

    PMID:19882669 PMID:20161774 PMID:20817733

    Open questions at the time
    • Which PiT1 domain mediates JNK/caspase-8 suppression unknown
    • Whether apoptosis protection explains the embryonic lethality not tested
  9. 2012 High

    Identifying EKLF as a direct transcriptional activator of PiT1 and showing that hematopoietic-specific PiT1 deletion causes cell-autonomous erythroid maturation defects placed PiT1 downstream of a master erythroid regulator.

    Evidence ChIP for EKLF at Pit1 promoter, hematopoietic conditional KO, fetal liver transplant, shRNA rescue in G1E cells

    PMID:23190530

    Open questions at the time
    • Whether the erythroid role is transport-dependent or -independent not resolved
    • PiT1 target genes in erythroid cells not defined
  10. 2017 High

    Demonstrating that PiT1 and PiT2 form Pi-regulated heterodimers that activate ERK1/2 independently of transport established a Pi-sensing mechanism, explaining how cells detect extracellular phosphate levels without requiring Pi import.

    Evidence BRET, cross-linking, Ser-128 mutagenesis, transport-deficient PiT mutants, ERK1/2 phosphorylation

    PMID:29233890

    Open questions at the time
    • Downstream effectors linking PiT1/PiT2 heterodimer to ERK1/2 not identified
    • Structural basis for Pi-induced conformational change unknown
  11. 2018 High

    Conditional PiT1 deletion in chondrocytes causing ER stress, impaired protein secretion, and reduced PDI reductase activity — rescued by transport-dead PiT1 — revealed an unexpected transport-independent role in ER homeostasis via direct PDI interaction.

    Evidence Chondrocyte-specific conditional KO mice, co-IP with PDI, PDI reductase assay, ER stress markers, rescue with transport-deficient mutant

    PMID:30347511

    Open questions at the time
    • How PiT1 reaches the ER (trafficking mechanism) uncharacterized
    • Whether PDI interaction is direct or mediated by a complex unknown
    • Generalizability of ER role to non-chondrocyte cells not shown
  12. 2019 High

    Showing that PiT1 and NF-κB form a positive feedback loop — p65 binds the Pit1 promoter while PiT1 promotes IκB degradation and p65 nuclear translocation — established PiT1 as an amplifier of macrophage inflammatory signaling.

    Evidence Macrophage-specific Pit1 conditional KO mice, ChIP for p65, luciferase reporter, IκB/p65 immunoblot upon LPS

    PMID:30755642

    Open questions at the time
    • Whether NF-κB role is transport-dependent or -independent not tested
    • Mechanism by which PiT1 promotes IκB degradation not defined
  13. 2020 High

    Combined Pit1/Pit2 deletion in skeletal muscle causing lethal atrophy with reduced ERK1/2 and AMPK activation demonstrated collective essentiality for myofiber survival, while zebrafish slc20a1a morphant kidney/cloaca defects linked PiT1 to urogenital development.

    Evidence Double conditional KO mice with physiological and signaling readouts; zebrafish morpholino knockdown; human variant analysis in BEEC patients

    PMID:32080237 PMID:32850778

    Open questions at the time
    • Individual contribution of PiT1 versus PiT2 in muscle not separated
    • Human SLC20A1 variants in BEEC lack functional validation beyond transport assay
    • Whether muscle phenotype is transport-dependent not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the high-resolution structure of PiT1, the identity of intracellular effectors linking PiT1 to p38 MAPK and JNK suppression, the trafficking mechanism directing PiT1 to the ER, and whether its transport-independent and transport-dependent roles can be genetically separated in vivo using knock-in transport-dead alleles.
  • No high-resolution 3D structure of PiT1
  • No knock-in transport-dead mouse model to separate functions in vivo
  • Intracellular signaling adaptor(s) coupling PiT1 cytoplasmic domains to MAPK cascades unidentified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0001618 virus receptor activity 4 GO:0005215 transporter activity 4 GO:0098772 molecular function regulator activity 3 GO:0140299 molecular sensor activity 1
Localization
GO:0005886 plasma membrane 4 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-1266738 Developmental Biology 4 R-HSA-382551 Transport of small molecules 4 R-HSA-1640170 Cell Cycle 1 R-HSA-168256 Immune System 1 R-HSA-5357801 Programmed Cell Death 1
Partners
EKLFPDISLC20A2
Complex memberships
PiT1–PiT2 heterodimer

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 PiT-1 (SLC20A1)-mediated phosphate uptake is required for vascular smooth muscle cell (VSMC) calcification and osteogenic phenotype change; knockdown of PiT-1 by siRNA blocked phosphate-induced calcification and suppressed induction of osteogenic markers Cbfa-1 and osteopontin, while overexpression restored calcification, demonstrating transport-dependent signaling. Stable siRNA knockdown in human SMCs, retroviral overexpression, sodium-dependent phosphate transport assays, osteogenic marker measurement Circulation Research High 16527991
2009 PiT1 has a transport-independent function in cell proliferation: PiT1 depletion in HeLa and HepG2 cells markedly reduces cell proliferation, delays cell cycle, and impairs mitosis/cytokinesis; non-transporting PiT1 mutants rescue proliferation of PiT1-depleted cells, and PiT1 depletion activates p38 MAPK specifically. RNA interference (transient and stable), cell cycle analysis, in vivo tumor xenograft in nude mice, rescue with non-transporting mutants, MAPK phosphorylation assays Journal of Biological Chemistry High 19726692
2010 PiT1 (SLC20A1) is essential for embryonic liver development and hematopoiesis in mice; complete PiT1 deletion causes embryonic lethality at E12.5 due to fetal liver hypoplasia, massive hepatic apoptosis, and consequent anemia, revealing a non-redundant in vivo role. Conditional and null allele mouse genetics, histology, hematopoietic progenitor transplantation experiments PloS One High 20161774
2010 PiT1 has a transport-independent anti-apoptotic function in TNF-induced apoptosis: PiT1-depleted cells are more sensitive to TNF-induced apoptosis with enhanced caspase-8 and sustained JNK activation; a Pi-uptake-deficient PiT1 mutant rescues this phenotype, demonstrating the function is independent of phosphate transport. siRNA depletion in HeLa cells and PiT1-/- MEFs, rescue with transport-dead PiT1 mutant, caspase-8 and JNK activation assays Journal of Biological Chemistry High 20817733
2017 PiT1 and PiT2 form Pi-regulated heterodimers that mediate extracellular phosphate sensing independently of phosphate transport; Pi-regulated heterodimerization depends on putative Pi-binding residue Ser-128 in PiT1, and both transporters are required for Pi-dependent ERK1/2 phosphorylation and downstream gene regulation. Cross-linking, bioluminescence resonance energy transfer (BRET), transport-deficient PiT mutants, ERK1/2 phosphorylation assays, conditional deletion Journal of Biological Chemistry High 29233890
2018 PiT1/Slc20a1 has a transport-independent role in endoplasmic reticulum homeostasis in chondrocytes: conditional PiT1 ablation causes ER stress, chondrocyte death, and intracellular retention of aggrecan and VEGF-A; PiT1 co-localizes with ER marker ERp46 rather than the plasma membrane and binds the ER chaperone PDI, impairing PDI reductase activity upon PiT1 loss. Conditional gene deletion in mice, ER stress markers (Chop, Atf4, Bip), co-localization with ERp46, co-immunoprecipitation with PDI, PDI reductase activity assay, rescue with transport-deficient PiT1 mutant Journal of Bone and Mineral Research High 30347511
2012 EKLF transcription factor drives PiT1 expression during erythroid maturation by directly binding the PiT1 promoter in vivo; hematopoietic-specific PiT1 deletion causes cell-autonomous erythroid maturation defects, and re-expression of PiT1 in EKLF-depleted cells partially restores maturation. Hematopoietic-specific conditional knockout mice, fetal liver transplantation, ChIP for EKLF binding to Pit1 promoter, shRNA depletion of PiT1 or EKLF in G1E cells, rescue by PiT1 re-expression Blood High 23190530
2006 BMP-2 selectively increases Pit-1 (but not Pit-2) mRNA and sodium-dependent Pi transport activity via the JNK pathway in osteoblast-like cells, and this enhanced Pi transport through Pit-1 is required for BMP-2-induced matrix mineralization, as shown by antisense Pit-1 and pharmacological Pi transport inhibition. Radiolabeled phosphate uptake assay, Northern blot for Pit-1/Pit-2 mRNA, antisense Pit-1 expression, JNK inhibitor, alizarin red mineralization assay Journal of Bone and Mineral Research High 16734382
2007 Osteoblast-autonomous Pi regulation via Pit1 is a rate-limiting step in bone mineralization: foscarnet (NaPi transport inhibitor) blocks mineralization in vitro and locally in vivo; Pit1 over- or underexpression bi-directionally regulates mineralization; stanniocalcin-1 is identified as an early response gene that increases Pit1 expression. In vivo calvarial injection of foscarnet, Pit1 over/underexpression in osteoblast cultures, gene expression analysis Molecular and Cellular Biology High 17438129
2009 PiT-1 (SLC20A1) conditional and null alleles in mice confirm that PiT-1 null embryos are lethal with defects in yolk sac vasculature and anemia, establishing a necessary, non-redundant in vivo role in embryonic development. Cre-loxP conditional knockout mouse generation, embryonic phenotype analysis Genesis High 19882669
2009 SLC20A1 topology was resolved by substituted cysteine accessibility mutagenesis (SCAM) in live cells, revealing a 12-transmembrane-helix structure with 7 extracellular regions, revising previous 10-TM models and defining the structural basis for viral receptor and transport functions. Substituted cysteine accessibility mutagenesis (SCAM), glycosylation mapping, HMMTOP computational modeling constrained by empirical data Journal of Biological Chemistry High 19717569
1993 Human SLC20A1 (GLVR1) residues 550–551 in a cluster at loop 4 are critical determinants for gibbon ape leukemia virus (GALV) infection; this region (region A) is highly polymorphic between species and determines species-specific viral receptor function. Chimeric human/mouse GLVR1 proteins, point mutagenesis, viral infection assays Journal of Virology High 8411375
2002 Region A (residues 550–558) of PiT1 is not the direct viral binding site for GALV/FeLV-B; a second region (residues 232–260, region B) is required for both viral entry and virus binding; region B mutations cause improper membrane orientation of PiT1, and compensatory region A mutations restore orientation and function. Epitope-tagged Pit1 proteins, virus binding assays, membrane topology analysis (glycosylation, epitope accessibility), mutagenesis Journal of Virology High 12097582
1998 Rat PiT-1 expressed in Xenopus oocytes functions as a Na+-dependent Pi cotransporter; its mRNA is regulated by dietary Pi and vitamin D in parathyroid glands, with lower PiT-1 mRNA in vitamin D-deficient rats and higher levels with low-Pi diet. Xenopus oocyte expression/Pi transport assay, Northern blot, dietary manipulation in rats Endocrinology High 9528951
2019 PiT1 promotes NF-κB-dependent inflammatory signaling in response to LPS: PiT1-deficient macrophages show impaired MCP-1 and IL-6 production; p65 directly binds the Pit1 promoter (by ChIP) and activates Pit1 transcription; PiT1 deficiency reduces IκB degradation and p65 nuclear translocation, establishing a PiT1/NF-κB positive feedback loop. Conditional macrophage-specific Pit1 knockout mice (Mx1-Cre), siRNA depletion, LPS stimulation, ChIP for p65 at Pit1 promoter, luciferase reporter assay, IκB/p65 western blot Scientific Reports High 30755642
2020 Simultaneous conditional deletion of both Pit1 and Pit2 in skeletal muscle causes atrophy and death by P13, demonstrating they are collectively essential for myofiber survival; gene-dose-dependent reduction in running activity and reduced ERK1/2 activation and AMP kinase stimulation indicate Pi transport-dependent metabolic sensing. Conditional double knockout mice (human skeletal actin-Cre), running activity assays, grip strength, ERK1/2 and AMPK western blot, C2C12 oxygen consumption assays Scientific Reports High 32080237
2013 Aldosterone upregulates PIT1 mRNA in human aortic smooth muscle cells, driving osteogenic transcription factor expression and ALP activity; spironolactone (mineralocorticoid receptor antagonist) and PIT1 siRNA silencing reverse these effects; FGF23 co-treatment mitigates aldosterone-induced PIT1 upregulation. siRNA knockdown of PIT1 in HAoSMCs, spironolactone treatment, gene expression assays, in vivo kl/kl mouse model Journal of Clinical Investigation High 23298834
1997 FeLV-B can use SLC20A1/Pit1 as a receptor; the N-terminal VRA region (aa 83–116) of FeLV-B SU is sufficient for Pit1 recognition in some cell types, while VRB (aa 146–249) provides a secondary determinant required for other cell types and for Pit2 usage. Chimeric FeLV-A/B SU envelope proteins, viral infection assays in multiple cell types Journal of Virology High 9343161
1998 A single amino acid insertion in region A (loop 4) of mouse Pit1 converts it into a functional amphotropic MLV (A-MuLV) receptor, demonstrating that region A determines receptor specificity for multiple gammaretroviruses. Point insertion mutagenesis of mouse Pit1, viral infection assays Journal of Virology High 9557753
2020 Morpholino knockdown of zebrafish slc20a1a causes kidney cysts and cloaca/hindgut malformations; de novo monoallelic SLC20A1 variants identified in bladder exstrophy-epispadias complex patients do not impair phosphate transport in HEK293 cells, suggesting a transport-independent developmental role. Morpholino knockdown in zebrafish, phosphate transport assay in HEK293 cells, immunohistochemistry in human embryo Frontiers in Cell and Developmental Biology Medium 32850778

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Role of the sodium-dependent phosphate cotransporter, Pit-1, in vascular smooth muscle cell calcification. Circulation research 359 16527991
1998 Signal-specific co-activator domain requirements for Pit-1 activation. Nature 240 9751061
1999 Reciprocal interactions of Pit1 and GATA2 mediate signaling gradient-induced determination of pituitary cell types. Cell 239 10367888
1991 Variable effects of phosphorylation of Pit-1 dictated by the DNA response elements. Science (New York, N.Y.) 192 1652153
2002 The Snell dwarf mutation Pit1(dw) can increase life span in mice. Mechanisms of ageing and development 165 11718806
1992 Mutations in the Pit-1 gene in children with combined pituitary hormone deficiency. Biochemical and biophysical research communications 140 1472057
2013 Spironolactone ameliorates PIT1-dependent vascular osteoinduction in klotho-hypomorphic mice. The Journal of clinical investigation 133 23298834
2006 Enhanced expression of the inorganic phosphate transporter Pit-1 is involved in BMP-2-induced matrix mineralization in osteoblast-like cells. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 126 16734382
2007 Osteoblast autonomous Pi regulation via Pit1 plays a role in bone mineralization. Molecular and cellular biology 105 17438129
2016 Silent subtype 3 pituitary adenomas are not always silent and represent poorly differentiated monomorphous plurihormonal Pit-1 lineage adenomas. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 102 26743473
2009 Identification of a novel function of PiT1 critical for cell proliferation and independent of its phosphate transport activity. The Journal of biological chemistry 98 19726692
2010 Phosphate and vascular calcification: Emerging role of the sodium-dependent phosphate co-transporter PiT-1. Thrombosis and haemostasis 94 20664908
1992 Hormonal regulation of the thyrotropin beta-subunit gene by phosphorylation of the pituitary-specific transcription factor Pit-1. Proceedings of the National Academy of Sciences of the United States of America 94 1321428
1992 Functional isoforms of Pit-1 generated by alternative messenger RNA splicing. Molecular endocrinology (Baltimore, Md.) 94 1569967
1998 Visualization of Pit-1 transcription factor interactions in the living cell nucleus by fluorescence resonance energy transfer microscopy. Molecular endocrinology (Baltimore, Md.) 91 9731708
2017 Phosphate (Pi)-regulated heterodimerization of the high-affinity sodium-dependent Pi transporters PiT1/Slc20a1 and PiT2/Slc20a2 underlies extracellular Pi sensing independently of Pi uptake. The Journal of biological chemistry 90 29233890
1998 Molecular cloning and hormonal regulation of PiT-1, a sodium-dependent phosphate cotransporter from rat parathyroid glands. Endocrinology 87 9528951
2010 The phosphate transporter PiT1 (Slc20a1) revealed as a new essential gene for mouse liver development. PloS one 86 20161774
1992 An alternatively spliced Pit-1 isoform altered in its ability to trans-activate. Nucleic acids research 82 1561093
2009 PROP1 coexists with SOX2 and induces PIT1-commitment cells. Biochemical and biophysical research communications 74 19442651
1994 Multiple Pit-1-binding sites facilitate estrogen responsiveness of the prolactin gene. Molecular endocrinology (Baltimore, Md.) 73 7708061
1991 Thyrotropin-releasing hormone action on the prolactin promoter is mediated by the POU protein pit-1. Molecular endocrinology (Baltimore, Md.) 70 1922085
1993 Definition of a domain of GLVR1 which is necessary for infection by gibbon ape leukemia virus and which is highly polymorphic between species. Journal of virology 67 8411375
2004 Zebrafish pit1 mutants lack three pituitary cell types and develop severe dwarfism. Molecular endocrinology (Baltimore, Md.) 66 14988429
2018 Breast cancer metastasis to liver and lung is facilitated by Pit-1-CXCL12-CXCR4 axis. Oncogene 64 29321662
1993 A thyrotrope-specific variant of Pit-1 transactivates the thyrotropin beta promoter. The Journal of biological chemistry 64 8407911
1995 A composite Ets/Pit-1 binding site in the prolactin gene can mediate transcriptional responses to multiple signal transduction pathways. The Journal of biological chemistry 62 7673116
1997 Three distinct envelope domains, variably present in subgroup B feline leukemia virus recombinants, mediate Pit1 and Pit2 receptor recognition. Journal of virology 61 9343161
1995 A novel E250X mutation of the PIT1 gene in a patient with combined pituitary hormone deficiency. Endocrine journal 59 7670563
1998 RNA levels of human retrovirus receptors Pit1 and Pit2 do not correlate with infectibility by three retroviral vector pseudotypes. Human gene therapy 56 9853528
2010 Identification of a novel transport-independent function of PiT1/SLC20A1 in the regulation of TNF-induced apoptosis. The Journal of biological chemistry 55 20817733
2002 Effects of the Pit1 mutation on the insulin signaling pathway: implications on the longevity of the long-lived Snell dwarf mouse. Mechanisms of ageing and development 55 12020946
1995 Association of PIT1 polymorphisms with growth and carcass traits in pigs. Journal of animal science 51 7665359
1998 Central hypothyroidism reveals compound heterozygous mutations in the Pit-1 gene. Hormone research 48 9485179
1998 Rarity of PIT1 involvement in children from Russia with combined pituitary hormone deficiency. American journal of medical genetics 48 9632165
2010 Deregulation of the Pit-1 transcription factor in human breast cancer cells promotes tumor growth and metastasis. The Journal of clinical investigation 46 21060149
1999 Subnuclear partitioning and functional regulation of the Pit-1 transcription factor. Journal of cellular biochemistry 44 10022514
1993 Analysis of Pit-1 in regulating mouse TSH beta promoter activity in thyrotropes. Molecular and cellular endocrinology 44 8276142
1996 Pit-1: clinical aspects. Hormone research 43 8805025
2009 Generation of mouse conditional and null alleles of the type III sodium-dependent phosphate cotransporter PiT-1. Genesis (New York, N.Y. : 2000) 42 19882669
2004 Regulation of phosphate (Pi) transport and NaPi-III transporter (Pit-1) mRNA in rat osteoblasts. The Journal of endocrinology 42 15171701
1992 Activin inhibits binding of transcription factor Pit-1 to the growth hormone promoter. Proceedings of the National Academy of Sciences of the United States of America 40 1454833
2012 NELL-1 increases pre-osteoblast mineralization using both phosphate transporter Pit1 and Pit2. Biochemical and biophysical research communications 38 22580275
1995 Pituitary-type transcription of the human prolactin gene in the absence of Pit-1. Molecular endocrinology (Baltimore, Md.) 35 7476971
2003 Clinical characteristics and molecular analysis of PIT1, PROP1,LHX3, and HESX1 in combined pituitary hormone deficiency patients with abnormal pituitary MR imaging. Hormone research 34 14646405
2000 Pituitary and extrapituitary growth hormone: Pit-1 dependence? Canadian journal of physiology and pharmacology 34 11149379
1993 Promoter activity of human renin 5'-flanking DNA sequences is activated by the pituitary-specific transcription factor Pit-1. The Journal of biological chemistry 34 8420924
2002 Reassessing the role of region A in Pit1-mediated viral entry. Journal of virology 33 12097582
1992 Structures of cDNAs encoding chum salmon pituitary-specific transcription factor, Pit-1/GHF-1. Gene 33 1634120
2007 Molecular analysis of PROP1, PIT1, HESX1, LHX3, and LHX4 shows high frequency of PROP1 mutations in patients with familial forms of combined pituitary hormone deficiency. Arquivos brasileiros de endocrinologia e metabologia 32 18157385
2005 Role of prophet of Pit1 (PROP1) in gonadotrope differentiation and puberty. Endocrinology 31 16384867
2024 Pituitary neuroendocrine tumors with PIT1/SF1 co-expression show distinct clinicopathological and molecular features. Acta neuropathologica 30 38228887
2018 PiT1/Slc20a1 Is Required for Endoplasmic Reticulum Homeostasis, Chondrocyte Survival, and Skeletal Development. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 30 30347511
2023 Single-cell sequencing of PIT1-positive pituitary adenoma highlights the pro-tumour microenvironment mediated by IFN-γ-induced tumour-associated fibroblasts remodelling. British journal of cancer 29 36631635
2013 Mice with hypomorphic expression of the sodium-phosphate cotransporter PiT1/Slc20a1 have an unexpected normal bone mineralization. PloS one 29 23785462
2019 Novel function of PiT1/SLC20A1 in LPS-related inflammation and wound healing. Scientific reports 28 30755642
2016 Calcium Overload Accelerates Phosphate-Induced Vascular Calcification Via Pit-1, but not the Calcium-Sensing Receptor. Journal of atherosclerosis and thrombosis 28 27840385
2008 Functions of PIT1 in GATA2-dependent transactivation of the thyrotropin beta promoter. Journal of molecular endocrinology 28 19103719
2006 The Na+/PO4 cotransporter SLC20A1 gene labels distinct restricted subdomains of the developing pronephros in Xenopus and zebrafish embryos. Gene expression patterns : GEP 28 16531124
2002 Domains of Pit-1 required for transcriptional synergy with GATA-2 on the TSH beta gene. Molecular and cellular endocrinology 28 12385825
2023 Multilineage Pituitary Neuroendocrine Tumors (PitNETs) Expressing PIT1 and SF1. Endocrine pathology 27 37268858
2009 Inorganic phosphate regulates Glvr-1 and -2 expression: role of calcium and ERK1/2. Biochemical and biophysical research communications 27 19232318
1998 Expression of the tissue-specific transcription factor Pit-1 in the lancelet, Branchiostoma lanceolatum. The Journal of comparative neurology 27 9511922
2016 Vitamin-D receptor agonist calcitriol reduces calcification in vitro through selective upregulation of SLC20A2 but not SLC20A1 or XPR1. Scientific reports 26 27184385
2009 Effects of transgenic Pit-1 overexpression on calcium phosphate and bone metabolism. Journal of bone and mineral metabolism 26 19795094
1996 In situ hybridization analysis of Pit-1 mRNA and hormonal production in human pituitary adenomas. Acta neuropathologica 26 8834538
1995 In vivo mutational analysis of the DNA binding domain of the tissue-specific transcription factor, Pit-1. The Journal of biological chemistry 26 7592721
2012 EKLF-driven PIT1 expression is critical for mouse erythroid maturation in vivo and in vitro. Blood 25 23190530
1993 Pit-1 and hypopituitarism. Trends in endocrinology and metabolism: TEM 25 18407138
2009 New structural arrangement of the extracellular regions of the phosphate transporter SLC20A1, the receptor for gibbon ape leukemia virus. The Journal of biological chemistry 24 19717569
2005 Association of PIT1, GH and GHRH polymorphisms with performance and carcass traits in Landrace pigs. Journal of applied genetics 24 15876687
2004 Immunolocalization of Pit-1 in gonadotroph nuclei is indicative of the transdifferentiation of gonadotroph to lactotroph cells in prolactinomas induced by estrogen. Histochemistry and cell biology 24 15221415
1996 Mechanisms of transcriptional activation of the promoter of the rainbow trout prolactin gene by GHF1/Pit1 and glucocorticoid. Biochemical and biophysical research communications 24 8694834
2020 SLC20A1 Is Involved in Urinary Tract and Urorectal Development. Frontiers in cell and developmental biology 23 32850778
2005 Absent or delayed adrenarche in Pit-1/POU1F1 deficiency. Hormone research 22 16210857
1996 Thyroid hormone receptor beta2 promoter activity in pituitary cells is regulated by Pit-1. The Journal of biological chemistry 22 8798664
1995 A dopamine-responsive domain in the N-terminal sequence of Pit-1. Transcriptional inhibition in endocrine cell types. The Journal of biological chemistry 22 7706253
2020 Slc20a1/Pit1 and Slc20a2/Pit2 are essential for normal skeletal myofiber function and survival. Scientific reports 21 32080237
2013 ox-LDL induces PiT-1 expression in human aortic valve interstitial cells. The Journal of surgical research 21 23849774
2008 The PIT1 gene polymorphisms were associated with chicken growth traits. BMC genetics 21 18304318
2017 Magnesium prevents phosphate-induced vascular calcification via TRPM7 and Pit-1 in an aortic tissue culture model. Hypertension research : official journal of the Japanese Society of Hypertension 20 28123180
2002 A novel mutation in PIT-1: phenotypic variability in familial combined pituitary hormone deficiencies. Journal of pediatric endocrinology & metabolism : JPEM 20 11924936
1998 Single amino acid insertion in loop 4 confers amphotropic murine leukemia virus receptor function upon murine Pit1. Journal of virology 20 9557753
1993 Pit-1 and pituitary function. The Journal of pediatric endocrinology 20 7920987
2021 PD-L1 Is Preferentially Expressed in PIT-1 Positive Pituitary Neuroendocrine Tumours. Endocrine pathology 19 33694064
2021 Phosphate Overload Stimulates Inflammatory Reaction via PiT-1 and Induces Vascular Calcification in Uremia. Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation 19 34688540
2019 LincRNA-SLC20A1 (SLC20A1) promotes extracellular matrix degradation in nucleus pulposus cells in human intervertebral disc degeneration by targeting the miR-31-5p/MMP3 axis. International journal of clinical and experimental pathology 19 31934214
2000 Biochemical and genetic characterization of the porcine Prophet of Pit-1 pituitary transcription factor. Molecular and cellular endocrinology 19 11064154
2021 High SLC20A1 Expression Is Associated With Poor Prognoses in Claudin-low and Basal-like Breast Cancers. Anticancer research 18 33419798
2005 The role of CBP/p300 interactions and Pit-1 dimerization in the pathophysiological mechanism of combined pituitary hormone deficiency. The Journal of clinical endocrinology and metabolism 18 16263824
1995 Activin increases phosphorylation and decreases stability of the transcription factor Pit-1 in MtTW15 somatotrope cells. The Journal of biological chemistry 18 7499395
2019 Spironolactone dose‑dependently alleviates the calcification of aortic rings cultured in hyperphosphatemic medium with or without hyperglycemia by suppressing phenotypic transition of VSMCs through downregulation of Pit‑1. Molecular medicine reports 17 30896801
2017 A novel thymoma-associated autoimmune disease: Anti-PIT-1 antibody syndrome. Scientific reports 17 28216655
2014 Cancer progression by breast tumors with Pit-1-overexpression is blocked by inhibition of metalloproteinase (MMP)-13. Breast cancer research : BCR 17 25527274
2005 EGF stimulates Pit-1 independent transcription of the human prolactin pituitary promoter in human breast cancer SK-BR-3 cells through its proximal AP-1 response element. Molecular and cellular endocrinology 17 15607537
1996 The ontogeny of pit-1 expression in the human fetal pituitary gland. Neuroendocrinology 17 8739890
1995 Screening for PIT1 abnormality by PCR direct sequencing method. Thyroid : official journal of the American Thyroid Association 17 7580269
1998 Synthesis of turkey Pit-1 mRNA variants by alternative splicing and transcription initiation. DNA and cell biology 16 9468226
1998 Retrovirus receptor PiT-1 of the Felis catus. Biochimica et biophysica acta 16 9878855
1995 Pit-1 exhibits a unique promoter spacing requirement for activation and synergism. The Journal of biological chemistry 16 7876215