Europe PMC

This website requires cookies, and the limited processing of your personal data in order to function. By using the site you are agreeing to this as outlined in our privacy notice and cookie policy.

The latent transforming growth factor beta binding protein (LTBP) family.

Author information

Affiliations

  • 1. Northwestern University Medical School, Lake Shore Center, Room 1707, 850 North Lake Shore Drive, Chicago, IL 60611, USA.
      Authors
    • Oklü R 1
    (1 author)

ORCIDs linked to this article

The Biochemical Journal, 01 Dec 2000, 352 Pt 3:601-610
https://doi.org/10.1042/bj3520601 PMID: 11104663 PMCID: PMC1221494

ReviewFree full text in Europe PMC

Abstract 

The transforming growth factor beta (TGFbeta) cytokines are a multi-functional family that exert a wide variety of effects on both normal and transformed mammalian cells. The secretion and activation of TGFbetas is regulated by their association with latency-associated proteins and latent TGFbeta binding proteins (LTBPs). Over the past few years, three members of the LTBP family have been identified, in addition to the protoype LTBP1 first sequenced in 1990. Three of the LTBP family are expressed in a variety of isoforms as a consequence of alternative splicing. This review summarizes the differences between the isoforms in terms of the effects on domain structure and hence possible function. The close identity between LTBPs and members of the fibrillin family, mutations in which have been linked directly to Marfan's syndrome, suggests that anomalous expression of LTBPs may be associated with disease. Recent data indicating that differential expression of LTBP1 isoforms occurs during the development of coronary heart disease is considered, together with evidence that modulation of LTBP function, and hence of TGFbeta activity, is associated with a variety of cancers.

Free full text 

Logo of biochemjLink to Publisher's site
Biochem J. 2000 Dec 15; 352(Pt 3): 601–610.
PMCID: PMC1221494
PMID: 11104663

The latent transforming growth factor beta binding protein (LTBP) family.

R Oklü and R Hesketh
Author information Copyright and License information Disclaimer

Abstract

The transforming growth factor beta (TGFbeta) cytokines are a multi-functional family that exert a wide variety of effects on both normal and transformed mammalian cells. The secretion and activation of TGFbetas is regulated by their association with latency-associated proteins and latent TGFbeta binding proteins (LTBPs). Over the past few years, three members of the LTBP family have been identified, in addition to the protoype LTBP1 first sequenced in 1990. Three of the LTBP family are expressed in a variety of isoforms as a consequence of alternative splicing. This review summarizes the differences between the isoforms in terms of the effects on domain structure and hence possible function. The close identity between LTBPs and members of the fibrillin family, mutations in which have been linked directly to Marfan's syndrome, suggests that anomalous expression of LTBPs may be associated with disease. Recent data indicating that differential expression of LTBP1 isoforms occurs during the development of coronary heart disease is considered, together with evidence that modulation of LTBP function, and hence of TGFbeta activity, is associated with a variety of cancers.

Full Text

The Full Text of this article is available as a PDF (218K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Olofsson A, Miyazono K, Kanzaki T, Colosetti P, Engström U, Heldin CH. Transforming growth factor-beta 1, -beta 2, and -beta 3 secreted by a human glioblastoma cell line. Identification of small and different forms of large latent complexes. J Biol Chem. 1992 Sep 25;267(27):19482–19488. [Abstract] [Google Scholar]
  • Miyazono K, Hellman U, Wernstedt C, Heldin CH. Latent high molecular weight complex of transforming growth factor beta 1. Purification from human platelets and structural characterization. J Biol Chem. 1988 May 5;263(13):6407–6415. [Abstract] [Google Scholar]
  • Wakefield LM, Smith DM, Flanders KC, Sporn MB. Latent transforming growth factor-beta from human platelets. A high molecular weight complex containing precursor sequences. J Biol Chem. 1988 Jun 5;263(16):7646–7654. [Abstract] [Google Scholar]
  • Kanzaki T, Olofsson A, Morén A, Wernstedt C, Hellman U, Miyazono K, Claesson-Welsh L, Heldin CH. TGF-beta 1 binding protein: a component of the large latent complex of TGF-beta 1 with multiple repeat sequences. Cell. 1990 Jun 15;61(6):1051–1061. [Abstract] [Google Scholar]
  • Okada F, Yamaguchi K, Ichihara A, Nakamura T. Purification and structural analysis of a latent form of transforming growth factor-beta from rat platelets. J Biochem. 1989 Aug;106(2):304–310. [Abstract] [Google Scholar]
  • Tsuji T, Okada F, Yamaguchi K, Nakamura T. Molecular cloning of the large subunit of transforming growth factor type beta masking protein and expression of the mRNA in various rat tissues. Proc Natl Acad Sci U S A. 1990 Nov;87(22):8835–8839. [Europe PMC free article] [Abstract] [Google Scholar]
  • Olofsson A, Ichijo H, Morén A, ten Dijke P, Miyazono K, Heldin CH. Efficient association of an amino-terminally extended form of human latent transforming growth factor-beta binding protein with the extracellular matrix. J Biol Chem. 1995 Dec 29;270(52):31294–31297. [Abstract] [Google Scholar]
  • Gibson MA, Hatzinikolas G, Davis EC, Baker E, Sutherland GR, Mecham RP. Bovine latent transforming growth factor beta 1-binding protein 2: molecular cloning, identification of tissue isoforms, and immunolocalization to elastin-associated microfibrils. Mol Cell Biol. 1995 Dec;15(12):6932–6942. [Europe PMC free article] [Abstract] [Google Scholar]
  • Morén A, Olofsson A, Stenman G, Sahlin P, Kanzaki T, Claesson-Welsh L, ten Dijke P, Miyazono K, Heldin CH. Identification and characterization of LTBP-2, a novel latent transforming growth factor-beta-binding protein. J Biol Chem. 1994 Dec 23;269(51):32469–32478. [Abstract] [Google Scholar]
  • Bashir MM, Han MD, Abrams WR, Tucker T, Ma RI, Gibson M, Ritty T, Mecham R, Rosenbloom J. Analysis of the human gene encoding latent transforming growth factor-beta-binding protein-2. Int J Biochem Cell Biol. 1996 May;28(5):531–542. [Abstract] [Google Scholar]
  • Fang J, Li X, Smiley E, Francke U, Mecham RP, Bonadio J. Mouse latent TGF-beta binding protein-2: molecular cloning and developmental expression. Biochim Biophys Acta. 1997 Nov 20;1354(3):219–230. [Abstract] [Google Scholar]
  • Yin W, Smiley E, Germiller J, Mecham RP, Florer JB, Wenstrup RJ, Bonadio J. Isolation of a novel latent transforming growth factor-beta binding protein gene (LTBP-3). J Biol Chem. 1995 Apr 28;270(17):10147–10160. [Abstract] [Google Scholar]
  • Li X, Yin W, Pérez-Jurado L, Bonadio J, Francke U. Mapping of human and murine genes for latent TGF-beta binding protein-2 (LTBP2). Mamm Genome. 1995 Jan;6(1):42–45. [Abstract] [Google Scholar]
  • Giltay R, Kostka G, Timpl R. Sequence and expression of a novel member (LTBP-4) of the family of latent transforming growth factor-beta binding proteins. FEBS Lett. 1997 Jul 14;411(2-3):164–168. [Abstract] [Google Scholar]
  • Massagué J. The transforming growth factor-beta family. Annu Rev Cell Biol. 1990;6:597–641. [Abstract] [Google Scholar]
  • de Larco JE, Todaro GJ. Growth factors from murine sarcoma virus-transformed cells. Proc Natl Acad Sci U S A. 1978 Aug;75(8):4001–4005. [Europe PMC free article] [Abstract] [Google Scholar]
  • Roberts AB, Lamb LC, Newton DL, Sporn MB, De Larco JE, Todaro GJ. Transforming growth factors: isolation of polypeptides from virally and chemically transformed cells by acid/ethanol extraction. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3494–3498. [Europe PMC free article] [Abstract] [Google Scholar]
  • Anzano MA, Roberts AB, Smith JM, Sporn MB, De Larco JE. Sarcoma growth factor from conditioned medium of virally transformed cells is composed of both type alpha and type beta transforming growth factors. Proc Natl Acad Sci U S A. 1983 Oct;80(20):6264–6268. [Europe PMC free article] [Abstract] [Google Scholar]
  • Nishio E, Watanabe Y. Transforming growth factor beta is a modulator of platelet-derived growth factor action in vascular smooth muscle cells: a possible role for catalase activity and glutathione peroxidase activity. Biochem Biophys Res Commun. 1997 Mar 6;232(1):1–4. [Abstract] [Google Scholar]
  • Siese A, Jaros PP, Willig A. Analysis of interleukin (IL)-1 beta and transforming growth factor (TGF)-beta-induced signal transduction pathways in IL-2 and TGF-beta secretion and proliferation in the thymoma cell line EL4.NOB-1. Scand J Immunol. 1999 Feb;49(2):139–148. [Abstract] [Google Scholar]
  • Ignotz RA, Massagué J. Transforming growth factor-beta stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix. J Biol Chem. 1986 Mar 25;261(9):4337–4345. [Abstract] [Google Scholar]
  • Roberts AB, Sporn MB, Assoian RK, Smith JM, Roche NS, Wakefield LM, Heine UI, Liotta LA, Falanga V, Kehrl JH, et al. Transforming growth factor type beta: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4167–4171. [Europe PMC free article] [Abstract] [Google Scholar]
  • Wahl SM, Hunt DA, Wakefield LM, McCartney-Francis N, Wahl LM, Roberts AB, Sporn MB. Transforming growth factor type beta induces monocyte chemotaxis and growth factor production. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5788–5792. [Europe PMC free article] [Abstract] [Google Scholar]
  • Wrann M, Bodmer S, de Martin R, Siepl C, Hofer-Warbinek R, Frei K, Hofer E, Fontana A. T cell suppressor factor from human glioblastoma cells is a 12.5-kd protein closely related to transforming growth factor-beta. EMBO J. 1987 Jun;6(6):1633–1636. [Europe PMC free article] [Abstract] [Google Scholar]
  • Gohongi T, Fukumura D, Boucher Y, Yun CO, Soff GA, Compton C, Todoroki T, Jain RK. Tumor-host interactions in the gallbladder suppress distal angiogenesis and tumor growth: involvement of transforming growth factor beta1. Nat Med. 1999 Oct;5(10):1203–1208. [Abstract] [Google Scholar]
  • Parsons-Wingerter P, Elliott KE, Farr AG, Radhakrishnan K, Clark JI, Sage EH. Generational analysis reveals that TGF-beta1 inhibits the rate of angiogenesis in vivo by selective decrease in the number of new vessels. Microvasc Res. 2000 Mar;59(2):221–232. [Abstract] [Google Scholar]
  • Bonewald LF, Dallas SL. Role of active and latent transforming growth factor beta in bone formation. J Cell Biochem. 1994 Jul;55(3):350–357. [Abstract] [Google Scholar]
  • Kimchi A, Wang XF, Weinberg RA, Cheifetz S, Massagué J. Absence of TGF-beta receptors and growth inhibitory responses in retinoblastoma cells. Science. 1988 Apr 8;240(4849):196–199. [Abstract] [Google Scholar]
  • Inagaki M, Moustakas A, Lin HY, Lodish HF, Carr BI. Growth inhibition by transforming growth factor beta (TGF-beta) type I is restored in TGF-beta-resistant hepatoma cells after expression of TGF-beta receptor type II cDNA. Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5359–5363. [Europe PMC free article] [Abstract] [Google Scholar]
  • Damstrup L, Rygaard K, Spang-Thomsen M, Skovgaard Poulsen H. Expression of transforming growth factor beta (TGF beta) receptors and expression of TGF beta 1, TGF beta 2 and TGF beta 3 in human small cell lung cancer cell lines. Br J Cancer. 1993 May;67(5):1015–1021. [Europe PMC free article] [Abstract] [Google Scholar]
  • Park K, Kim SJ, Bang YJ, Park JG, Kim NK, Roberts AB, Sporn MB. Genetic changes in the transforming growth factor beta (TGF-beta) type II receptor gene in human gastric cancer cells: correlation with sensitivity to growth inhibition by TGF-beta. Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):8772–8776. [Europe PMC free article] [Abstract] [Google Scholar]
  • Glick AB, Kulkarni AB, Tennenbaum T, Hennings H, Flanders KC, O'Reilly M, Sporn MB, Karlsson S, Yuspa SH. Loss of expression of transforming growth factor beta in skin and skin tumors is associated with hyperproliferation and a high risk for malignant conversion. Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6076–6080. [Europe PMC free article] [Abstract] [Google Scholar]
  • Jirtle RL, Haag JD, Ariazi EA, Gould MN. Increased mannose 6-phosphate/insulin-like growth factor II receptor and transforming growth factor beta 1 levels during monoterpene-induced regression of mammary tumors. Cancer Res. 1993 Sep 1;53(17):3849–3852. [Abstract] [Google Scholar]
  • Blobe GC, Schiemann WP, Lodish HF. Role of transforming growth factor beta in human disease. N Engl J Med. 2000 May 4;342(18):1350–1358. [Abstract] [Google Scholar]
  • Sun L, Wu G, Willson JK, Zborowska E, Yang J, Rajkarunanayake I, Wang J, Gentry LE, Wang XF, Brattain MG. Expression of transforming growth factor beta type II receptor leads to reduced malignancy in human breast cancer MCF-7 cells. J Biol Chem. 1994 Oct 21;269(42):26449–26455. [Abstract] [Google Scholar]
  • Villanueva A, García C, Paules AB, Vicente M, Megías M, Reyes G, de Villalonga P, Agell N, Lluís F, Bachs O, et al. Disruption of the antiproliferative TGF-beta signaling pathways in human pancreatic cancer cells. Oncogene. 1998 Oct 15;17(15):1969–1978. [Abstract] [Google Scholar]
  • Grady WM, Myeroff LL, Swinler SE, Rajput A, Thiagalingam S, Lutterbaugh JD, Neumann A, Brattain MG, Chang J, Kim SJ, et al. Mutational inactivation of transforming growth factor beta receptor type II in microsatellite stable colon cancers. Cancer Res. 1999 Jan 15;59(2):320–324. [Abstract] [Google Scholar]
  • Hojo M, Morimoto T, Maluccio M, Asano T, Morimoto K, Lagman M, Shimbo T, Suthanthiran M. Cyclosporine induces cancer progression by a cell-autonomous mechanism. Nature. 1999 Feb 11;397(6719):530–534. [Abstract] [Google Scholar]
  • Cui W, Fowlis DJ, Bryson S, Duffie E, Ireland H, Balmain A, Akhurst RJ. TGFbeta1 inhibits the formation of benign skin tumors, but enhances progression to invasive spindle carcinomas in transgenic mice. Cell. 1996 Aug 23;86(4):531–542. [Abstract] [Google Scholar]
  • Grainger DJ, Metcalfe JC. A pivotal role for TGF-beta in atherogenesis? Biol Rev Camb Philos Soc. 1995 Nov;70(4):571–596. [Abstract] [Google Scholar]
  • Grainger DJ, Kemp PR, Liu AC, Lawn RM, Metcalfe JC. Activation of transforming growth factor-beta is inhibited in transgenic apolipoprotein(a) mice. Nature. 1994 Aug 11;370(6489):460–462. [Abstract] [Google Scholar]
  • Grainger DJ, Kemp PR, Metcalfe JC, Liu AC, Lawn RM, Williams NR, Grace AA, Schofield PM, Chauhan A. The serum concentration of active transforming growth factor-beta is severely depressed in advanced atherosclerosis. Nat Med. 1995 Jan;1(1):74–79. [Abstract] [Google Scholar]
  • Grainger DJ, Mosedale DE, Metcalfe JC. TGF-beta in blood: a complex problem. Cytokine Growth Factor Rev. 2000 Mar-Jun;11(1-2):133–145. [Abstract] [Google Scholar]
  • Corson GM, Chalberg SC, Dietz HC, Charbonneau NL, Sakai LY. Fibrillin binds calcium and is coded by cDNAs that reveal a multidomain structure and alternatively spliced exons at the 5' end. Genomics. 1993 Aug;17(2):476–484. [Abstract] [Google Scholar]
  • Koski C, Saharinen J, Keski-Oja J. Independent promoters regulate the expression of two amino terminally distinct forms of latent transforming growth factor-beta binding protein-1 (LTBP-1) in a cell type-specific manner. J Biol Chem. 1999 Nov 12;274(46):32619–32630. [Abstract] [Google Scholar]
  • Gleizes PE, Beavis RC, Mazzieri R, Shen B, Rifkin DB. Identification and characterization of an eight-cysteine repeat of the latent transforming growth factor-beta binding protein-1 that mediates bonding to the latent transforming growth factor-beta1. J Biol Chem. 1996 Nov 22;271(47):29891–29896. [Abstract] [Google Scholar]
  • Saharinen J, Taipale J, Keski-Oja J. Association of the small latent transforming growth factor-beta with an eight cysteine repeat of its binding protein LTBP-1. EMBO J. 1996 Jan 15;15(2):245–253. [Europe PMC free article] [Abstract] [Google Scholar]
  • Yin W, Fang J, Smiley E, Bonadio J. 8-Cysteine TGF-BP structural motifs are the site of covalent binding between mouse LTBP-3, LTBP-2, and latent TGF-beta 1. Biochim Biophys Acta. 1998 Apr 2;1383(2):340–350. [Abstract] [Google Scholar]
  • Yuan X, Downing AK, Knott V, Handford PA. Solution structure of the transforming growth factor beta-binding protein-like module, a domain associated with matrix fibrils. EMBO J. 1997 Nov 17;16(22):6659–6666. [Europe PMC free article] [Abstract] [Google Scholar]
  • Rosenbloom J, Abrams WR, Mecham R. Extracellular matrix 4: the elastic fiber. FASEB J. 1993 Oct;7(13):1208–1218. [Abstract] [Google Scholar]
  • Sakai LY, Keene DR, Engvall E. Fibrillin, a new 350-kD glycoprotein, is a component of extracellular microfibrils. J Cell Biol. 1986 Dec;103(6 Pt 1):2499–2509. [Europe PMC free article] [Abstract] [Google Scholar]
  • Zhang H, Apfelroth SD, Hu W, Davis EC, Sanguineti C, Bonadio J, Mecham RP, Ramirez F. Structure and expression of fibrillin-2, a novel microfibrillar component preferentially located in elastic matrices. J Cell Biol. 1994 Mar;124(5):855–863. [Europe PMC free article] [Abstract] [Google Scholar]
  • Colosetti P, Hellman U, Heldin CH, Miyazono K. Ca2+ binding of latent transforming growth factor-beta 1 binding protein. FEBS Lett. 1993 Apr 5;320(2):140–144. [Abstract] [Google Scholar]
  • Reinhardt DP, Mechling DE, Boswell BA, Keene DR, Sakai LY, Bächinger HP. Calcium determines the shape of fibrillin. J Biol Chem. 1997 Mar 14;272(11):7368–7373. [Abstract] [Google Scholar]
  • Reinhardt DP, Ono RN, Notbohm H, Müller PK, Bächinger HP, Sakai LY. Mutations in calcium-binding epidermal growth factor modules render fibrillin-1 susceptible to proteolysis. A potential disease-causing mechanism in Marfan syndrome. J Biol Chem. 2000 Apr 21;275(16):12339–12345. [Abstract] [Google Scholar]
  • Saharinen J, Taipale J, Monni O, Keski-Oja J. Identification and characterization of a new latent transforming growth factor-beta-binding protein, LTBP-4. J Biol Chem. 1998 Jul 17;273(29):18459–18469. [Abstract] [Google Scholar]
  • Oklü R, Metcalfe JC, Hesketh TR, Kemp PR. Loss of a consensus heparin binding site by alternative splicing of latent transforming growth factor-beta binding protein-1. FEBS Lett. 1998 Mar 27;425(2):281–285. [Abstract] [Google Scholar]
  • Oklü R, Hesketh TR, Metcalfe JC, Kemp PR. Expression of alternatively spliced human latent transforming growth factor beta binding protein-1. FEBS Lett. 1998 Sep 18;435(2-3):143–148. [Abstract] [Google Scholar]
  • Gong W, Roth S, Michel K, Gressner AM. Isoforms and splice variant of transforming growth factor beta-binding protein in rat hepatic stellate cells. Gastroenterology. 1998 Feb;114(2):352–363. [Abstract] [Google Scholar]
  • Yin W, Smiley E, Bonadio J. Alternative splicing of LTBP-3. Biochem Biophys Res Commun. 1998 Apr 17;245(2):454–458. [Abstract] [Google Scholar]
  • Adès LC, Haan EA, Colley AF, Richard RI. Characterisation of four novel fibrillin-1 (FBN1) mutations in Marfan syndrome. J Med Genet. 1996 Aug;33(8):665–671. [Europe PMC free article] [Abstract] [Google Scholar]
  • Dietz HC, Valle D, Francomano CA, Kendzior RJ, Jr, Pyeritz RE, Cutting GR. The skipping of constitutive exons in vivo induced by nonsense mutations. Science. 1993 Jan 29;259(5095):680–683. [Abstract] [Google Scholar]
  • Liu W, Qian C, Francke U. Silent mutation induces exon skipping of fibrillin-1 gene in Marfan syndrome. Nat Genet. 1997 Aug;16(4):328–329. [Abstract] [Google Scholar]
  • Nunes I, Gleizes PE, Metz CN, Rifkin DB. Latent transforming growth factor-beta binding protein domains involved in activation and transglutaminase-dependent cross-linking of latent transforming growth factor-beta. J Cell Biol. 1997 Mar 10;136(5):1151–1163. [Europe PMC free article] [Abstract] [Google Scholar]
  • Poltorak Z, Cohen T, Sivan R, Kandelis Y, Spira G, Vlodavsky I, Keshet E, Neufeld G. VEGF145, a secreted vascular endothelial growth factor isoform that binds to extracellular matrix. J Biol Chem. 1997 Mar 14;272(11):7151–7158. [Abstract] [Google Scholar]
  • Rebay I, Fleming RJ, Fehon RG, Cherbas L, Cherbas P, Artavanis-Tsakonas S. Specific EGF repeats of Notch mediate interactions with Delta and Serrate: implications for Notch as a multifunctional receptor. Cell. 1991 Nov 15;67(4):687–699. [Abstract] [Google Scholar]
  • Fülöp C, Walcz E, Valyon M, Glant TT. Expression of alternatively spliced epidermal growth factor-like domains in aggrecans of different species. Evidence for a novel module. J Biol Chem. 1993 Aug 15;268(23):17377–17383. [Abstract] [Google Scholar]
  • Smas CM, Green D, Sul HS. Structural characterization and alternate splicing of the gene encoding the preadipocyte EGF-like protein pref-1. Biochemistry. 1994 Aug 9;33(31):9257–9265. [Abstract] [Google Scholar]
  • Liu W, Qian C, Comeau K, Brenn T, Furthmayr H, Francke U. Mutant fibrillin-1 monomers lacking EGF-like domains disrupt microfibril assembly and cause severe marfan syndrome. Hum Mol Genet. 1996 Oct;5(10):1581–1587. [Abstract] [Google Scholar]
  • Miyazono K, Olofsson A, Colosetti P, Heldin CH. A role of the latent TGF-beta 1-binding protein in the assembly and secretion of TGF-beta 1. EMBO J. 1991 May;10(5):1091–1101. [Europe PMC free article] [Abstract] [Google Scholar]
  • Dallas SL, Park-Snyder S, Miyazono K, Twardzik D, Mundy GR, Bonewald LF. Characterization and autoregulation of latent transforming growth factor beta (TGF beta) complexes in osteoblast-like cell lines. Production of a latent complex lacking the latent TGF beta-binding protein. J Biol Chem. 1994 Mar 4;269(9):6815–6821. [Abstract] [Google Scholar]
  • Koli K, Keski-Oja J. 1,25-Dihydroxyvitamin D3 enhances the expression of transforming growth factor beta 1 and its latent form binding protein in cultured breast carcinoma cells. Cancer Res. 1995 Apr 1;55(7):1540–1546. [Abstract] [Google Scholar]
  • Miyazono K, Thyberg J, Heldin CH. Retention of the transforming growth factor-beta 1 precursor in the Golgi complex in a latent endoglycosidase H-sensitive form. J Biol Chem. 1992 Mar 15;267(8):5668–5675. [Abstract] [Google Scholar]
  • Kirschenlohr HL, Metcalfe JC, Weissberg PL, Grainger DJ. Adult human aortic smooth muscle cells in culture produce active TGF-beta. Am J Physiol. 1993 Aug;265(2 Pt 1):C571–C576. [Abstract] [Google Scholar]
  • Kirschenlohr HL, Metcalfe JC, Weissberg PL, Grainger DJ. Proliferation of human aortic vascular smooth muscle cells in culture is modulated by active TGF beta. Cardiovasc Res. 1995 Jun;29(6):848–855. [Abstract] [Google Scholar]
  • Sato Y, Rifkin DB. Inhibition of endothelial cell movement by pericytes and smooth muscle cells: activation of a latent transforming growth factor-beta 1-like molecule by plasmin during co-culture. J Cell Biol. 1989 Jul;109(1):309–315. [Europe PMC free article] [Abstract] [Google Scholar]
  • Flaumenhaft R, Abe M, Sato Y, Miyazono K, Harpel J, Heldin CH, Rifkin DB. Role of the latent TGF-beta binding protein in the activation of latent TGF-beta by co-cultures of endothelial and smooth muscle cells. J Cell Biol. 1993 Feb;120(4):995–1002. [Europe PMC free article] [Abstract] [Google Scholar]
  • Dennis PA, Rifkin DB. Cellular activation of latent transforming growth factor beta requires binding to the cation-independent mannose 6-phosphate/insulin-like growth factor type II receptor. Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):580–584. [Europe PMC free article] [Abstract] [Google Scholar]
  • Kovacina KS, Steele-Perkins G, Purchio AF, Lioubin M, Miyazono K, Heldin CH, Roth RA. Interactions of recombinant and platelet transforming growth factor-beta 1 precursor with the insulin-like growth factor II/mannose 6-phosphate receptor. Biochem Biophys Res Commun. 1989 Apr 14;160(1):393–403. [Abstract] [Google Scholar]
  • Wang S, Souza RF, Kong D, Yin J, Smolinski KN, Zou TT, Frank T, Young J, Flanders KC, Sugimura H, et al. Deficient transforming growth factor-beta1 activation and excessive insulin-like growth factor II (IGFII) expression in IGFII receptor-mutant tumors. Cancer Res. 1997 Jul 1;57(13):2543–2546. [Abstract] [Google Scholar]
  • Purchio AF, Cooper JA, Brunner AM, Lioubin MN, Gentry LE, Kovacina KS, Roth RA, Marquardt H. Identification of mannose 6-phosphate in two asparagine-linked sugar chains of recombinant transforming growth factor-beta 1 precursor. J Biol Chem. 1988 Oct 5;263(28):14211–14215. [Abstract] [Google Scholar]
  • Brunner AM, Gentry LE, Cooper JA, Purchio AF. Recombinant type 1 transforming growth factor beta precursor produced in Chinese hamster ovary cells is glycosylated and phosphorylated. Mol Cell Biol. 1988 May;8(5):2229–2232. [Europe PMC free article] [Abstract] [Google Scholar]
  • Miyazono K, Heldin CH. Role for carbohydrate structures in TGF-beta 1 latency. Nature. 1989 Mar 9;338(6211):158–160. [Abstract] [Google Scholar]
  • Taipale J, Saharinen J, Hedman K, Keski-Oja J. Latent transforming growth factor-beta 1 and its binding protein are components of extracellular matrix microfibrils. J Histochem Cytochem. 1996 Aug;44(8):875–889. [Abstract] [Google Scholar]
  • Raghunath M, Unsöld C, Kubitscheck U, Bruckner-Tuderman L, Peters R, Meuli M. The cutaneous microfibrillar apparatus contains latent transforming growth factor-beta binding protein-1 (LTBP-1) and is a repository for latent TGF-beta1. J Invest Dermatol. 1998 Oct;111(4):559–564. [Abstract] [Google Scholar]
  • Munger JS, Harpel JG, Gleizes PE, Mazzieri R, Nunes I, Rifkin DB. Latent transforming growth factor-beta: structural features and mechanisms of activation. Kidney Int. 1997 May;51(5):1376–1382. [Abstract] [Google Scholar]
  • Sato Y, Okada F, Abe M, Seguchi T, Kuwano M, Sato S, Furuya A, Hanai N, Tamaoki T. The mechanism for the activation of latent TGF-beta during co-culture of endothelial cells and smooth muscle cells: cell-type specific targeting of latent TGF-beta to smooth muscle cells. J Cell Biol. 1993 Dec;123(5):1249–1254. [Europe PMC free article] [Abstract] [Google Scholar]
  • Yang Y, Dignam JD, Gentry LE. Role of carbohydrate structures in the binding of beta1-latency-associated peptide to ligands. Biochemistry. 1997 Sep 30;36(39):11923–11932. [Abstract] [Google Scholar]
  • Taipale J, Miyazono K, Heldin CH, Keski-Oja J. Latent transforming growth factor-beta 1 associates to fibroblast extracellular matrix via latent TGF-beta binding protein. J Cell Biol. 1994 Jan;124(1-2):171–181. [Europe PMC free article] [Abstract] [Google Scholar]
  • Verderio E, Gaudry C, Gross S, Smith C, Downes S, Griffin M. Regulation of cell surface tissue transglutaminase: effects on matrix storage of latent transforming growth factor-beta binding protein-1. J Histochem Cytochem. 1999 Nov;47(11):1417–1432. [Abstract] [Google Scholar]
  • Kojima S, Nara K, Rifkin DB. Requirement for transglutaminase in the activation of latent transforming growth factor-beta in bovine endothelial cells. J Cell Biol. 1993 Apr;121(2):439–448. [Europe PMC free article] [Abstract] [Google Scholar]
  • Nunes I, Shapiro RL, Rifkin DB. Characterization of latent TGF-beta activation by murine peritoneal macrophages. J Immunol. 1995 Aug 1;155(3):1450–1459. [Abstract] [Google Scholar]
  • Dallas SL, Miyazono K, Skerry TM, Mundy GR, Bonewald LF. Dual role for the latent transforming growth factor-beta binding protein in storage of latent TGF-beta in the extracellular matrix and as a structural matrix protein. J Cell Biol. 1995 Oct;131(2):539–549. [Europe PMC free article] [Abstract] [Google Scholar]
  • 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 Jan 13;136(1):193–204. [Europe PMC free article] [Abstract] [Google Scholar]
  • Grainger DJ, Kirschenlohr HL, Metcalfe JC, Weissberg PL, Wade DP, Lawn RM. Proliferation of human smooth muscle cells promoted by lipoprotein(a). Science. 1993 Jun 11;260(5114):1655–1658. [Abstract] [Google Scholar]
  • Carmeliet P, Schoonjans L, Kieckens L, Ream B, Degen J, Bronson R, De Vos R, van den Oord JJ, Collen D, Mulligan RC. Physiological consequences of loss of plasminogen activator gene function in mice. Nature. 1994 Mar 31;368(6470):419–424. [Abstract] [Google Scholar]
  • Shull MM, Ormsby I, Kier AB, Pawlowski S, Diebold RJ, Yin M, Allen R, Sidman C, Proetzel G, Calvin D, et al. Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease. Nature. 1992 Oct 22;359(6397):693–699. [Europe PMC free article] [Abstract] [Google Scholar]
  • Shipley JM, Mecham RP, Maus E, Bonadio J, Rosenbloom J, McCarthy RT, Baumann ML, Frankfater C, Segade F, Shapiro SD. Developmental expression of latent transforming growth factor beta binding protein 2 and its requirement early in mouse development. Mol Cell Biol. 2000 Jul;20(13):4879–4887. [Europe PMC free article] [Abstract] [Google Scholar]
  • Crawford SE, Stellmach V, Murphy-Ullrich JE, Ribeiro SM, Lawler J, Hynes RO, Boivin GP, Bouck N. Thrombospondin-1 is a major activator of TGF-beta1 in vivo. Cell. 1998 Jun 26;93(7):1159–1170. [Abstract] [Google Scholar]
  • Hyytiäinen M, Taipale J, Heldin CH, Keski-Oja J. Recombinant latent transforming growth factor beta-binding protein 2 assembles to fibroblast extracellular matrix and is susceptible to proteolytic processing and release. J Biol Chem. 1998 Aug 7;273(32):20669–20676. [Abstract] [Google Scholar]
  • Majesky MW, Lindner V, Twardzik DR, Schwartz SM, Reidy MA. Production of transforming growth factor beta 1 during repair of arterial injury. J Clin Invest. 1991 Sep;88(3):904–910. [Europe PMC free article] [Abstract] [Google Scholar]
  • Kanzaki T, Tamura K, Takahashi K, Saito Y, Akikusa B, Oohashi H, Kasayuki N, Ueda M, Morisaki N. In vivo effect of TGF- beta 1. Enhanced intimal thickening by administration of TGF- beta 1 in rabbit arteries injured with a balloon catheter. Arterioscler Thromb Vasc Biol. 1995 Nov;15(11):1951–1957. [Abstract] [Google Scholar]
  • Smith JD, Bryant SR, Couper LL, Vary CP, Gotwals PJ, Koteliansky VE, Lindner V. Soluble transforming growth factor-beta type II receptor inhibits negative remodeling, fibroblast transdifferentiation, and intimal lesion formation but not endothelial growth. Circ Res. 1999 May 28;84(10):1212–1222. [Abstract] [Google Scholar]
  • Nabel EG, Shum L, Pompili VJ, Yang ZY, San H, Shu HB, Liptay S, Gold L, Gordon D, Derynck R, et al. Direct transfer of transforming growth factor beta 1 gene into arteries stimulates fibrocellular hyperplasia. Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10759–10763. [Europe PMC free article] [Abstract] [Google Scholar]
  • Schulick AH, Taylor AJ, Zuo W, Qiu CB, Dong G, Woodward RN, Agah R, Roberts AB, Virmani R, Dichek DA. Overexpression of transforming growth factor beta1 in arterial endothelium causes hyperplasia, apoptosis, and cartilaginous metaplasia. Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):6983–6988. [Europe PMC free article] [Abstract] [Google Scholar]
  • Wolf YG, Rasmussen LM, Ruoslahti E. Antibodies against transforming growth factor-beta 1 suppress intimal hyperplasia in a rat model. J Clin Invest. 1994 Mar;93(3):1172–1178. [Europe PMC free article] [Abstract] [Google Scholar]
  • Grainger DJ, Kemp PR, Witchell CM, Weissberg PL, Metcalfe JC. Transforming growth factor beta decreases the rate of proliferation of rat vascular smooth muscle cells by extending the G2 phase of the cell cycle and delays the rise in cyclic AMP before entry into M phase. Biochem J. 1994 Apr 1;299(Pt 1):227–235. [Europe PMC free article] [Abstract] [Google Scholar]
  • Metcalfe JC, Grainger DJ. Transforming growth factor-beta and the protection from cardiovascular injury hypothesis. Biochem Soc Trans. 1995 May;23(2):403–406. [Abstract] [Google Scholar]
  • Williams JK, Wagner JD, Li Z, Golden DL, Adams MR. Tamoxifen inhibits arterial accumulation of LDL degradation products and progression of coronary artery atherosclerosis in monkeys. Arterioscler Thromb Vasc Biol. 1997 Feb;17(2):403–408. [Abstract] [Google Scholar]
  • Grainger DJ, Witchell CM, Metcalfe JC. Tamoxifen elevates transforming growth factor-beta and suppresses diet-induced formation of lipid lesions in mouse aorta. Nat Med. 1995 Oct;1(10):1067–1073. [Abstract] [Google Scholar]
  • Reckless J, Metcalfe JC, Grainger DJ. Tamoxifen decreases cholesterol sevenfold and abolishes lipid lesion development in apolipoprotein E knockout mice. Circulation. 1997 Mar 18;95(6):1542–1548. [Abstract] [Google Scholar]
  • McDonald CC, Stewart HJ. Fatal myocardial infarction in the Scottish adjuvant tamoxifen trial. The Scottish Breast Cancer Committee. BMJ. 1991 Aug 24;303(6800):435–437. [Europe PMC free article] [Abstract] [Google Scholar]
  • Van Laethem JL, Resibois A, Adler M, Peny MO, Ohtani H, Robberecht P. Localization of transforming growth factor-beta 1 precursor and latent TGF-beta 1 binding protein in colorectal adenomas. Dig Dis Sci. 1996 Sep;41(9):1741–1748. [Abstract] [Google Scholar]
  • Eklöv S, Funa K, Nordgren H, Olofsson A, Kanzaki T, Miyazono K, Nilsson S. Lack of the latent transforming growth factor beta binding protein in malignant, but not benign prostatic tissue. Cancer Res. 1993 Jul 1;53(13):3193–3197. [Abstract] [Google Scholar]
  • Chaudhry A, Oberg K, Gobl A, Heldin CH, Funa K. Expression of transforming growth factors beta 1, beta 2, beta 3 in neuroendocrine tumors of the digestive system. Anticancer Res. 1994 Sep-Oct;14(5B):2085–2091. [Abstract] [Google Scholar]
  • Van Laethem JL, Resibois A, Rickaert F, Devière J, Gelin M, Cremer M, Robberecht P. Different expression of transforming growth factor beta 1 in pancreatic ductal adenocarcinoma and cystic neoplasms. Pancreas. 1997 Jul;15(1):41–47. [Abstract] [Google Scholar]
  • Henriksen R, Gobl A, Wilander E, Oberg K, Miyazono K, Funa K. Expression and prognostic significance of TGF-beta isotypes, latent TGF-beta 1 binding protein, TGF-beta type I and type II receptors, and endoglin in normal ovary and ovarian neoplasms. Lab Invest. 1995 Aug;73(2):213–220. [Abstract] [Google Scholar]
  • Mizoi T, Ohtani H, Miyazono K, Miyazawa M, Matsuno S, Nagura H. Immunoelectron microscopic localization of transforming growth factor beta 1 and latent transforming growth factor beta 1 binding protein in human gastrointestinal carcinomas: qualitative difference between cancer cells and stromal cells. Cancer Res. 1993 Jan 1;53(1):183–190. [Abstract] [Google Scholar]
  • Karonen T, Jeskanen L, Keski-Oja J. Transforming growth factor beta 1 and its latent form binding protein-1 associate with elastic fibres in human dermis: accumulation in actinic damage and absence in anetoderma. Br J Dermatol. 1997 Jul;137(1):51–58. [Abstract] [Google Scholar]
  • van Laethem JL, Deviere J, Resibois A, Rickaert F, Vertongen P, Ohtani H, Cremer M, Miyazono K, Robberecht P. Localization of transforming growth factor beta 1 and its latent binding protein in human chronic pancreatitis. Gastroenterology. 1995 Jun;108(6):1873–1881. [Abstract] [Google Scholar]
  • Taketazu F, Kato M, Gobl A, Ichijo H, ten Dijke P, Itoh J, Kyogoku M, Rönnelid J, Miyazono K, Heldin CH, et al. Enhanced expression of transforming growth factor-beta s and transforming growth factor-beta type II receptor in the synovial tissues of patients with rheumatoid arthritis. Lab Invest. 1994 May;70(5):620–630. [Abstract] [Google Scholar]
  • Nakayama M, Okuda S, Tamaki K, Shimizu F, Kawachi H, Ando T, Yanagida T, Fujishima M. Roles of TGF-beta and latent TGF-beta-binding protein in glomerulosclerosis induced by two consecutive injections of monoclonal antibody 1-22-3 in rats. Nephron. 1997;76(1):82–89. [Abstract] [Google Scholar]
  • Wada T, Hamakawa S, Hori Y, Kaname S, Shimizu S, Kurokawa K, Katoh T. Immunohistochemical localization of latent transforming growth factor-beta binding protein in IgA nephropathy. Kidney Int Suppl. 1997 Dec;63:S182–S184. [Abstract] [Google Scholar]
  • Tamaki K, Okuda S, Miyazono K, Nakayama M, Fujishima M. Matrix-associated latent TGF-beta with latent TGF-beta binding protein in the progressive process in adriamycin-induced nephropathy. Lab Invest. 1995 Jul;73(1):81–89. [Abstract] [Google Scholar]
  • Tamaki K, Okuda S, Nakayama M, Yanagida T, Fujishima M. Transforming growth factor-beta 1 in hypertensive renal injury in Dahl salt-sensitive rats. J Am Soc Nephrol. 1996 Dec;7(12):2578–2589. [Abstract] [Google Scholar]
  • Hori Y, Katoh T, Hirakata M, Joki N, Kaname S, Fukagawa M, Okuda T, Ohashi H, Fujita T, Miyazono K, et al. Anti-latent TGF-beta binding protein-1 antibody or synthetic oligopeptides inhibit extracellular matrix expression induced by stretch in cultured rat mesangial cells. Kidney Int. 1998 Jun;53(6):1616–1625. [Abstract] [Google Scholar]
  • Yamazaki M, Minota S, Sakurai H, Miyazono K, Yamada A, Kanazawa I, Kawai M. Expression of transforming growth factor-beta 1 and its relation to endomysial fibrosis in progressive muscular dystrophy. Am J Pathol. 1994 Feb;144(2):221–226. [Europe PMC free article] [Abstract] [Google Scholar]
  • Waltenberger J, Lundin L, Oberg K, Wilander E, Miyazono K, Heldin CH, Funa K. Involvement of transforming growth factor-beta in the formation of fibrotic lesions in carcinoid heart disease. Am J Pathol. 1993 Jan;142(1):71–78. [Europe PMC free article] [Abstract] [Google Scholar]
  • Maeda J, Ueki N, Ohkawa T, Iwahashi N, Nakano T, Hada T, Higashino K. Local production and localization of transforming growth factor-beta in tuberculous pleurisy. Clin Exp Immunol. 1993 Apr;92(1):32–38. [Abstract] [Google Scholar]
  • Stenman G, Sahlin P, Olofsson A, Geurts van Kessel A, Miyazono K. Assignment of the gene encoding the latent TGF-beta 1-binding protein (LTBP1) to human chromosome 2, region p12-->q22. Cytogenet Cell Genet. 1994;66(2):117–119. [Abstract] [Google Scholar]
Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

Full text links 

Read article at publisher's site: https://doi.org/10.1042/bj3520601

Read article for free, from open access legal sources, via Unpaywall: https://europepmc.org/articles/pmc1221494?pdf=renderUnpaywall

Citations & impact 

Impact metrics

106
Citations
Jump to Citations
14
Data citations
Jump to Data

Citations of article over time

Alternative metrics

Altmetric item for https://www.altmetric.com/details/3496609
Altmetric
Discover the attention surrounding your research
https://www.altmetric.com/details/3496609
Altmetric item for https://www.altmetric.com/details/5443988
Altmetric
Discover the attention surrounding your research
https://www.altmetric.com/details/5443988

Smart citations by scite.ai
Smart citations by scite.ai include citation statements extracted from the full text of the citing article. The number of the statements may be higher than the number of citations provided by EuropePMC if one paper cites another multiple times or lower if scite has not yet processed some of the citing articles.
Explore citation contexts and check if this article has been supported or disputed.
https://scite.ai/reports/10.1042/bj3520601

Supporting
Mentioning
Contrasting
0
8
0

Article citations

Go to all (106) article citations

Other citations

Data 

Data behind the article

This data has been text mined from the article, or deposited into data resources.

BioStudies: supplemental material and supporting data

Similar Articles 

To arrive at the top five similar articles we use a word-weighted algorithm to compare words from the Title and Abstract of each citation.