Gene Symbol: Ltbp1
Description: latent transforming growth factor beta binding protein 1
Alias: 9430031G15Rik, 9830146M04, Ltbp-1, Ltbp1L, TGF-beta1-BP-1, Tgfb, b2b1000Clo, latent-transforming growth factor beta-binding protein 1, latent TGF beta binding protein, latent transforming growth factor beta binding protein 1L, transforming growth factor beta-1-binding protein 1
Species: mouse
Products:     Ltbp1

Top Publications

  1. Nakajima Y, Miyazono K, Kato M, Takase M, Yamagishi T, Nakamura H. Extracellular fibrillar structure of latent TGF beta binding protein-1: role in TGF beta-dependent endothelial-mesenchymal transformation during endocardial cushion tissue formation in mouse embryonic heart. J Cell Biol. 1997;136:193-204 pubmed
    ..These results suggest that LTBP-1 exists as an extracellular fibrillar structure and plays a role in the storage of TGF beta as a large latent TGF beta complex. ..
  2. Drews F, Knöbel S, Moser M, Muhlack K, Mohren S, Stoll C, et al. Disruption of the latent transforming growth factor-beta binding protein-1 gene causes alteration in facial structure and influences TGF-beta bioavailability. Biochim Biophys Acta. 2008;1783:34-48 pubmed
    ..Therefore, we conclude that LTBP-1 has essential functions in the control of TGF-beta activation. ..
  3. Todorovic V, Frendewey D, Gutstein D, Chen Y, Freyer L, Finnegan E, et al. Long form of latent TGF-beta binding protein 1 (Ltbp1L) is essential for cardiac outflow tract septation and remodeling. Development. 2007;134:3723-32 pubmed
    ..the in vivo role of Ltbp1 in mouse development, at the time when only the L isoform is expressed, we mutated the Ltbp1L locus by gene targeting...
  4. Yoshinaga K, Obata H, Jurukovski V, Mazzieri R, Chen Y, Zilberberg L, et al. Perturbation of transforming growth factor (TGF)-beta1 association with latent TGF-beta binding protein yields inflammation and tumors. Proc Natl Acad Sci U S A. 2008;105:18758-63 pubmed publisher
    ..Moreover, although mechanisms exist to activate latent TGF-beta1 in the absence of LTBP, these mechanisms are not as efficient as those that use the latent complex containing LTBP. ..
  5. Noguera I, Obata H, Gualandris A, Cowin P, Rifkin D. Molecular cloning of the mouse Ltbp-1 gene reveals tissue specific expression of alternatively spliced forms. Gene. 2003;308:31-41 pubmed
    ..The Ltbp-1 gene contains 34 exons and shows a similar organization to the LTBP-2 gene, suggesting that these genes originated from a common ancestral gene. ..
  6. Saharinen J, Hyytiäinen M, Taipale J, Keski Oja J. Latent transforming growth factor-beta binding proteins (LTBPs)--structural extracellular matrix proteins for targeting TGF-beta action. Cytokine Growth Factor Rev. 1999;10:99-117 pubmed
    ..The significance of this structural diversity is mostly unclear at present. ..
  7. Rifkin D. Latent transforming growth factor-beta (TGF-beta) binding proteins: orchestrators of TGF-beta availability. J Biol Chem. 2005;280:7409-12 pubmed
  8. Mazzieri R, Jurukovski V, Obata H, Sung J, Platt A, Annes E, et al. Expression of truncated latent TGF-beta-binding protein modulates TGF-beta signaling. J Cell Sci. 2005;118:2177-87 pubmed
  9. Chandramouli A, Simundza J, PINDERHUGHES A, Hiremath M, Droguett G, Frendewey D, et al. Ltbp1L is focally induced in embryonic mammary mesenchyme, demarcates the ductal luminal lineage and is upregulated during involution. Breast Cancer Res. 2013;15:R111 pubmed publisher
    ..To address this we have examined Ltbp1 promoter activity throughout mammary development using an Ltbp1L-LacZ reporter as well as expression of both Ltbp1L and 1S mRNA and protein by qRT-PCR, immunofluorescence and flow ..

More Information


  1. Roderburg C, Luedde M, Vargas Cardenas D, Vucur M, Mollnow T, Zimmermann H, et al. miR-133a mediates TGF-?-dependent derepression of collagen synthesis in hepatic stellate cells during liver fibrosis. J Hepatol. 2013;58:736-42 pubmed publisher
    ..Evidence is presented for a novel antifibrotic functional role of miR-133a in hepatofibrogenesis. miR-133a may thus represent a target for diagnostic and therapeutic strategies in liver fibrosis. ..
  2. Altmann C, Chang C, Munoz Sanjuan I, Bell E, Heke M, Rifkin D, et al. The latent-TGFbeta-binding-protein-1 (LTBP-1) is expressed in the organizer and regulates nodal and activin signaling. Dev Biol. 2002;248:118-27 pubmed
    ..These results indicate that LTBP-1 may be part of the regulatory system that establishes the threshold of morphogen activity for activins and nodals in the dorsal side of the embryo during gastrulation. ..
  3. Gomez Duran A, Carvajal Gonzalez J, Mulero Navarro S, Santiago Josefat B, Puga A, Fernandez Salguero P. Fitting a xenobiotic receptor into cell homeostasis: how the dioxin receptor interacts with TGFbeta signaling. Biochem Pharmacol. 2009;77:700-12 pubmed publisher
    ..We will integrate ECM proteases in the AhR-LTBP-1-TGFbeta axis and suggest a model that could help explain some in vivo phenotypes associated to AhR deficiency. ..
  4. Ono R, Sengle G, Charbonneau N, Carlberg V, Bachinger H, Sasaki T, et al. Latent transforming growth factor beta-binding proteins and fibulins compete for fibrillin-1 and exhibit exquisite specificities in binding sites. J Biol Chem. 2009;284:16872-81 pubmed publisher
    ..These studies also suggest that the fibulins may affect matrix sequestration of LTBPs, because in vitro interactions between these proteins are competitive. ..
  5. Yin W, Smiley E, Germiller J, Mecham R, Florer J, Wenstrup R, et al. Isolation of a novel latent transforming growth factor-beta binding protein gene (LTBP-3). J Biol Chem. 1995;270:10147-60 pubmed
    ..Bonadio, J., and Francke, U. (1995) Mamm. Genome 6, 42-45). Identification of a third binding protein provides further insight into a mechanism by which latent TGF-beta complexes can be targeted to connective tissue matrices and cells. ..
  6. Edwards J, Fujii H, Zhou A, Creemers J, Unutmaz D, Shevach E. Regulation of the expression of GARP/latent TGF-β1 complexes on mouse T cells and their role in regulatory T cell and Th17 differentiation. J Immunol. 2013;190:5506-15 pubmed publisher
    ..Induction of both Th17-producing cells and Tregs is caused preferentially by Tregs expressing the latent TGF-β1/GARP complex on their cell surface rather than by secreted latent TGF-β1. ..
  7. Koli K, Ryynänen M, Keski Oja J. Latent TGF-beta binding proteins (LTBPs)-1 and -3 coordinate proliferation and osteogenic differentiation of human mesenchymal stem cells. Bone. 2008;43:679-88 pubmed publisher
    ..Our results provide evidence that LTBP isoforms can differentially regulate TGF-beta activation and ECM accumulation during osteogenic differentiation. ..
  8. Mullen A, Orlando D, Newman J, Lovén J, Kumar R, Bilodeau S, et al. Master transcription factors determine cell-type-specific responses to TGF-? signaling. Cell. 2011;147:565-76 pubmed publisher
    ..We conclude that cell-type-specific master transcription factors determine the genes bound by Smad2/3 and are thus responsible for orchestrating the cell-type-specific effects of TGF-? signaling. ..
  9. Lucas C, Workman C, Beyaz S, Locascio S, Zhao G, Vignali D, et al. LAG-3, TGF-?, and cell-intrinsic PD-1 inhibitory pathways contribute to CD8 but not CD4 T-cell tolerance induced by allogeneic BMT with anti-CD40L. Blood. 2011;117:5532-40 pubmed publisher
    ..Finally, we uncovered a requirement for TGF-? signaling into T cells to achieve peripheral CD8 but not CD4 T-cell tolerance in this in vivo system. ..
  10. Weidenaar A, Ter Elst A, Kampen K, Meeuwsen de Boer T, de Jonge H, Scherpen F, et al. Stromal interaction essential for vascular endothelial growth factor A-induced tumour growth via transforming growth factor-? signalling. Br J Cancer. 2011;105:1856-63 pubmed publisher
    ..These results suggest a role for VEGFA-driven tumour growth by TGF-? signalling inhibition via paracrine mechanisms in vivo, and underscore the importance of stromal interaction in the VEGFA-induced phenotype. ..
  11. Heber Katz E, Chen P, Clark L, Zhang X, Troutman S, Blankenhorn E. Regeneration in MRL mice: further genetic loci controlling the ear hole closure trait using MRL and M.m. Castaneus mice. Wound Repair Regen. 2004;12:384-92 pubmed
    ..In addition, we report three new healing QTL. Furthermore, in this strain combination, we note a strong sexual dimorphism also observed in the MRL x C57BL/6 cross, both in the healing trait and in the QTL that control it. ..
  12. Nicklas D, Saiz L. Computational modelling of Smad-mediated negative feedback and crosstalk in the TGF-? superfamily network. J R Soc Interface. 2013;10:20130363 pubmed publisher
  13. Weiskirchen R, Moser M, Günther K, Weiskirchen S, Gressner A. The murine latent transforming growth factor-beta binding protein (Ltbp-1) is alternatively spliced, and maps to a region syntenic to human chromosome 2p21-22. Gene. 2003;308:43-52 pubmed
    ..The utilization of different promoters and their evolutionarily conservation further emphasize the complex regulation of Ltbp-1. ..
  14. Zingariello M, Martelli F, Ciaffoni F, Masiello F, Ghinassi B, D Amore E, et al. Characterization of the TGF-?1 signaling abnormalities in the Gata1low mouse model of myelofibrosis. Blood. 2013;121:3345-63 pubmed publisher
    ..These data identify altered expression signatures of TGF-?1 signaling that may be responsible for MF in Gata1(low) mice and may represent additional targets for therapeutic intervention in PMF. ..
  15. Horiguchi M, Todorovic V, Hadjiolova K, Weiskirchen R, Rifkin D. Abrogation of both short and long forms of latent transforming growth factor-β binding protein-1 causes defective cardiovascular development and is perinatally lethal. Matrix Biol. 2015;43:61-70 pubmed publisher
    ..There is controversy regarding the importance of LTBP-1L, as Ltbp1L knockout mice showed multiple cardiovascular defects but the complete null mice did not...
  16. Town T, Laouar Y, Pittenger C, Mori T, Szekely C, Tan J, et al. Blocking TGF-beta-Smad2/3 innate immune signaling mitigates Alzheimer-like pathology. Nat Med. 2008;14:681-7 pubmed publisher
    ..Taken together, our results suggest that blockade of TGF-beta-Smad2/3 signaling in peripheral macrophages represents a new therapeutic target for Alzheimer's disease. ..
  17. Ge G, Greenspan D. BMP1 controls TGFbeta1 activation via cleavage of latent TGFbeta-binding protein. J Cell Biol. 2006;175:111-20 pubmed
    ..We provide in vitro and in vivo evidence that BMP1 cleaves LTBP1 at two specific sites, thus liberating LLC from ECM and resulting in consequent activation of TGFbeta1 via ..
  18. Gomez Duran A, Ballestar E, Carvajal Gonzalez J, Marlowe J, Puga A, Esteller M, et al. Recruitment of CREB1 and histone deacetylase 2 (HDAC2) to the mouse Ltbp-1 promoter regulates its constitutive expression in a dioxin receptor-dependent manner. J Mol Biol. 2008;380:1-16 pubmed publisher
    ..Thus, epigenetics can contribute to constitutive Ltbp-1 repression by a mechanism requiring AhR activity. ..
  19. Kurohara K, Komatsu K, Kurisaki T, Masuda A, Irie N, Asano M, et al. Essential roles of Meltrin beta (ADAM19) in heart development. Dev Biol. 2004;267:14-28 pubmed
    ..These results suggest the necessity of proteolytic regulation of ErbB ligands by Meltrin beta for proper heart development. ..
  20. Gui Y, Murphy L. Interaction of insulin-like growth factor binding protein-3 with latent transforming growth factor-beta binding protein-1. Mol Cell Biochem. 2003;250:189-95 pubmed
    ..These data demonstrate that IGFBP-3 can bind to LTBP-1 and provide a potential mechanism whereby IGFBP-3 can interact with the TGF-beta system. ..
  21. Oklu R, Hesketh R. The latent transforming growth factor beta binding protein (LTBP) family. Biochem J. 2000;352 Pt 3:601-10 pubmed
    ..Over the past few years, three members of the LTBP family have been identified, in addition to the protoype LTBP1 first sequenced in 1990...
  22. Todorovic V, Finnegan E, Freyer L, Zilberberg L, Ota M, Rifkin D. Long form of latent TGF-? binding protein 1 (Ltbp1L) regulates cardiac valve development. Dev Dyn. 2011;240:176-87 pubmed publisher
    ..The long form of Latent TGF-? binding protein 1 (LTBP1L) covalently binds all TGF-? isoforms and regulates their bioavailability...
  23. Lorda Diez C, Montero J, Garcia Porrero J, Hurle J. Tgfbeta2 and 3 are coexpressed with their extracellular regulator Ltbp1 in the early limb bud and modulate mesodermal outgrowth and BMP signaling in chicken embryos. BMC Dev Biol. 2010;10:69 pubmed publisher
    ..Furthermore, we show that Latent Tgfbeta Binding protein 1 (LTBP1), which is a key extracellular modulator of Tgfbeta ligand bioavailability, is coexpressed with Tgfbetas in the ..
  24. Pandey P, Qin S, Ho J, Zhou J, Kreidberg J. Systems biology approach to identify transcriptome reprogramming and candidate microRNA targets during the progression of polycystic kidney disease. BMC Syst Biol. 2011;5:56 pubmed publisher
    ..miRNAs are small, regulatory non-coding RNAs, implicated in a wide spectrum of biological processes. Their expression levels are altered in several diseases including kidney cancer, diabetic nephropathy and PKD...
  25. Fontana L, Chen Y, Prijatelj P, Sakai T, Fassler R, Sakai L, et al. Fibronectin is required for integrin alphavbeta6-mediated activation of latent TGF-beta complexes containing LTBP-1. FASEB J. 2005;19:1798-808 pubmed
    ..The results indicate specificity for integrin-mediated latent TGF-beta activation that include unique sequences in LTBP-1 and an appropriate matrix molecule. ..
  26. Dallas S, Sivakumar P, Jones C, Chen Q, Peters D, Mosher D, et al. Fibronectin regulates latent transforming growth factor-beta (TGF beta) by controlling matrix assembly of latent TGF beta-binding protein-1. J Biol Chem. 2005;280:18871-80 pubmed
    ..Here we show that fibronectin is critical for the incorporation of LTBP1 and transforming growth factor-beta (TGF beta) into the ECM of osteoblasts and fibroblasts...
  27. Nakajima Y, Miyazono K, Nakamura H. Immunolocalization of latent transforming growth factor-beta binding protein-1 (LTBP1) during mouse development: possible roles in epithelial and mesenchymal cytodifferentiation. Cell Tissue Res. 1999;295:257-67 pubmed
    Latent transforming growth factor-beta binding protein-1 (LTBP1) is a member of the fibrillin family; it is a glycoprotein of more than 190 kDa that is characterized by its possession of 16-18 epidermal growth factor-like motifs and 8 ..
  28. Hubmacher D, Wang L, Mecham R, Reinhardt D, Apte S. Adamtsl2 deletion results in bronchial fibrillin microfibril accumulation and bronchial epithelial dysplasia--a novel mouse model providing insights into geleophysic dysplasia. Dis Model Mech. 2015;8:487-99 pubmed publisher
    ..ADAMTSL2 has been previously shown to bind FBN1 and latent TGFβ-binding protein-1 (LTBP1). Here, we investigated mice with targeted Adamtsl2 inactivation as a new model for GD (Adamtsl2(-/-) mice)...
  29. Dietzel E, Weiskirchen S, Floehr J, Horiguchi M, Todorovic V, Rifkin D, et al. Latent TGF-? binding protein-1 deficiency decreases female fertility. Biochem Biophys Res Commun. 2017;482:1387-1392 pubmed publisher
    ..The LTBP1 gene forms two major transcript variants (i.e. Ltbp1S and Ltbp1L) that are derived from different promoters...