Advertisement

Cytotechnology

, Volume 2, Issue 4, pp 307–316 | Cite as

Transforming growth factor-β receptors

  • Patricia R. Segarini
Article

Abstract

Transforming growth factor beta (TGF-β) binds specifically and with high affinity to several different cell surface proteins. Low Mr proteins of 50,000 and 80,000 have been termed type I and type II receptors. Intermediate sized binding components of 115,000–140,000 Mr and a high binding components of approximately 250,000 Mr in subunit size have been termed type III receptors. The high Mr component is a proteoglycan containing the glycosaminoglycan chains of heparan sulfate and chondroitin sulfate and the intermediate sized components are its core proteins. Although almost all cells have TGF-β receptors, binding of TGF-β to the type III binding components is restricted to cells of fibroblastic, osteoblastic and chondroblastic origin. The physiological relevance of each individual binding class is unclear. However, recent data indicate that the type III protein does not transmit signals to inhibit cell proliferation, induce protein synthesis, or promote cytomorphological change and that these activities may be mediated through the type I receptor. The mechanism of signal transduction remains unknown, but it does not appear to be associated with tyrosine phosphorylation or phosphorylation of the 40s ribosomal protein S6.

Key words

binding proteins proteoglycan receptors TGF-ß 

Abbreviations

TGF

Transforming Growth Factor

GAG

Glycosaminoglycan

EGF

Epidermal Growth Factor

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Anzano MA, Roberts AB, Smith JM, Sporn MB and Delarco JE (1983) Sarcoma growth factor from conditional medium of virally transformed cells is composed of both type α and type β transforming growth factors. Proc. Natl. Acad. Sci. USA 80: 6264–6268.Google Scholar
  2. 2.
    Balza E, Borsi L, Allemanni G and Zardi L (1988) Transforming growth factor β regulates the levels of different fibronectin isoforms in normal human cultured fibroblasts. FEBS Lett. 228: 42–44.Google Scholar
  3. 3.
    Bassols A and Massagué J (1988) Transforming growth factor β regulates the expression and structure of extracellular matrix chondroitin/dermatan sulfate proteoglycans J. Biol. Chem. 263: 3039–3045.Google Scholar
  4. 4.
    Bowen-Pope DF and Ross R (1982) Platelet-derived growth factor. Specific binding to target cells. J. Biol. Chem. 257: 5161–5171.Google Scholar
  5. 5.
    Boyd FT and Massagué F (1989) Transforming growth factor-β inhibition of epithelial cell proliferation linked to the expression of a 53-kDa membrane receptor. J. Biol. Chem. 264: 2272–2278.Google Scholar
  6. 6.
    Carpenter G, Lembach KJ, Morrison MM and Cohen S (1945) Characterization of the binding of 125I-labeled epidermal growth factor to human fibroblasts. J. Biol. Chem. 250: 4297–4304.Google Scholar
  7. 7.
    Cheiftez S, Like B and Massagué J (1986) Cellular distribution for the type I and type II receptors for transforming growth factor-β. J. Biol. Chem. 261: 9972–9978.Google Scholar
  8. 8.
    Cheiftez S, Weatherbee JA, Tsang M L-S Anderson JK, Mole JE, Lucas R and Massagué J (1987) The transforming growth factor-β system, a complex pattern of cross-reactive ligands and receptors. Cell 48: 409–415Google Scholar
  9. 9.
    Cheiftez S, Andres JL and Massagué J (1988a) The transforming growth factor-β receptor type III is a membrane proteoglycan. Domain structure of the receptor. J. Biol. Chem. 263: 16984–16991.Google Scholar
  10. 10.
    Cheifetz S, Bassols A, Stanley K, Ohta M, Greenberger J and Massagué J (1988b) Heterodimeric transforming growth factor β. Biological properties and interaction with three types of cell surface receptors. J. Biol. Chem. 263: 10783–10789.Google Scholar
  11. 11.
    Cheifetz S, Ling N, Guillemin R and Massagué J (1988c) A surface component on GH3 pituitary cells that recognizes transforming growth factor-β, activin, and inhibin. J. Biol. 263: 17225–17228.Google Scholar
  12. 12.
    Chen J-K, Hoshi H and McKeehan WL (1987) Transforming growth factor type β specifically stimulates synthesis of proteoglycan in human adult arterial smooth muscle cells. Proc. Natl. Acad. Sci. USA 84: 5287–5291.Google Scholar
  13. 13.
    Cochet C, Feige J-J and Chambaz EM (1988) Bovine adrenocortical cells exhibit high affinity transforming growth factor-β receptors which are regulated by adrenocorticotropin. J. Biol. Chem. 263: 5707–5713.Google Scholar
  14. 14.
    Delarco JE and Todaro GI (1978) Growth factors from murine sarcoma virus-transformed cells. Proc. Natl. Acad. Sci. USA 75: 4001–4005.Google Scholar
  15. 15.
    Edwards DR, Murphy G, Reynolds JJ, Whitham SE, Docherty AJP, Angel P and Heath JK (1987) Transforming growth factor beta modulates the expression of collagenase and metalloproteinase inhibitor. EMBO J. 6: 1899–1904.Google Scholar
  16. 16.
    Ewton DZ, Spizz G, Olson EN and Florini JR (1988) Decrease in transforming growth factor-β binding and action during differentiation in muscle cells. J. Biol. Chem. 263: 4029–4032.Google Scholar
  17. 17.
    Elford PR, Guenther HL, Felix R, Cecchini MG and Fleisch H (1987) Transforming growth factor-β reduces the phenotypic expression of osteoblastic MC3T3-E1 cells in monolayer culture. Bone 8: 259–262.Google Scholar
  18. 18.
    Ellingsworth LR, Nakayama D, Segarini P, Dasch J, Carrillo P and Waegell W (1988) Transforming growth factor-βs are equipotent growth inhibitors of interleukin-1-induced thymocyte proliferation. Cell. Immunol. 114: 41–54.Google Scholar
  19. 19.
    Ellingsworth L, Nakayama D, Dasch J, Segarini P, Carrillo P and Wagell W (1989) Transforming growth factor-beta 1 (TGF-β1) receptor complex expression on resting and nitrogen activated T cells. J. Cell. Biochem. 39: 489–500.Google Scholar
  20. 20.
    Fangor BO, Wakefield LM and Sporn MB (1986) Structure and properties of the cellular receptor for transforming growth factor type-beta. Biochemistry 25: 3083–3091.Google Scholar
  21. 21.
    Fine A and Goldstein RH (1987) The effect of transforming growth factor-β on cell proliferation and collagen formation by lung fibroblasts. J. Biol. Chem. 262: 3897–3902.Google Scholar
  22. 22.
    Flanders KC, Thompson NL, Cissel DS, Van Obberghen-Schilling E, Baker CC, Kass ME, Ellingsworth LR, Roberts AB and Sporn MB (1989) Transforming growth factor β1; Histochemical localization with antibodies to different epitopes. J. Cell Biol. 108: 653–660.Google Scholar
  23. 23.
    Florini JR, Roberts AB, Ewton DZ, Falen SL, Flanders KC and Sporn MB (1986) Transforming growth factor-β. A very potent inhibitor of myoblast differentiation, identical to the differentiation inhibitor secreted by Buffalo rat liver cells. J. Biol. Chem. 261: 16509–16513.Google Scholar
  24. 24.
    Frolik CA, Wakefield LM, Smith DM, and Sporn MB (1984) Characterization of a membrane receptor for transforming growth factor-β in normal rat kidney fibroblasts. J. Biol. Chem. 259: 10995–11000.Google Scholar
  25. 25.
    Heine UI, Munoz EF, Flanders KC, Ellingsworth LM, Lam H-Y P, Thompson NL, Roberts AB, and Sporn MB (1987) Role of transforming growth factor-β in the development of the mouse embryo. J. Cell Biol. 105: 2861–2876.Google Scholar
  26. 26.
    Heino J, Ignotz RA, Hemier ME, Crouse C and Massagué J (1989) Regulation of cell adhesion receptors by transforming growth factor-β. Concomitant regulation of integrins that share a common β subunit. J. Biol. Chem. 264: 380–388.Google Scholar
  27. 27.
    Heldin G-H, Wasteson A and Westermart B (1982) Interaction of platelet-derived growth factor with its fibroblast receptor: Demonstration of ligand degradation and receptor modulation. J. Biol. Chem. 257: 4216–4221.Google Scholar
  28. 28.
    Ignotz RA and Massagué J (1985) Type β transforming growth factor controls the adipogenic differentiation of 3T3 fibroblasts. Proc. Natl. Acad. Sci. USA 82: 8530–8534.Google Scholar
  29. 29.
    Ignotz RA and Massagué J (1986) Transforming growth factor-β stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix. J. Cell Biol. 261: 4337–4345.Google Scholar
  30. 30.
    Ignotz RA and Massagué J (1987) Cell adhesion protein receptors as targets for transforming growth factor-β action. Cell 51: 189–197.Google Scholar
  31. 31.
    Ignotz RA, Endo T and Massagué J (1987) Regulation of fibronectin and type I collagen mRNA levels by transforming growth factor-β. J. Biol. Chem. 262: 6443–6446.Google Scholar
  32. 32.
    Ignotz RA, Heino J and Massagué J (1989) Regulation of cell adhesion receptors by transforming growth factor-β. Regulation of vitronectin receptor and LFA-1. J. Biol. Chem. 264: 389–392.Google Scholar
  33. 33.
    Jakowlew SB, Dillard PJ, Kandaiah P, Sporn MB, Roberts AB (1988) complementary deoxyribonucleic acid cloning of a novel transforming growth factor-β messenger ribonucleic acid from chick embryo chondrocytes: Mol. Endocrinol. 2: 747–755.Google Scholar
  34. 34.
    Jakowlew SB, Dillard BI, Sporn MB and Roberts AB (1988b) Complementary deoxyribonucleic acid cloning of a messenger ribonucleic acid encoding transforming growth factor β4 from chicken embryo chondrocytes. Mol. Endocrinol. 2: 1186–1195.Google Scholar
  35. 35.
    Kinchi A, Wang X-F, Weinberg RA, Cheifetz S and Massagué J (1988) Absence of TGF-β receptors and growth inhibitory responses in retinoblastoma cells. Science 240: 196–199.Google Scholar
  36. 36.
    Kyprianou N and Isaacs JT (1988) Identification of a cellular receptor for transforming growth factor-β in rat ventral prostate and its negative regulation by androgens. Endocrinol. 123: 2124–2131.Google Scholar
  37. 37.
    Laiho M, Saksela O, Andreasen PA and Keski-Oja J (1986) Enhanced production and extracellular deposition of the endothelial-type plasminogen activator inhibitor in cultured human lung fibroblasts by transforming growth factor-β. J. Cell Biol. 103: 2403–2410.Google Scholar
  38. 38.
    Libby J, Martinez R and Weber MI (1986) Tyrosine phosphorylation in cells treated with transforming growth factor-β. J. Cell. Phys. 129: 159–166.Google Scholar
  39. 39.
    Like B and Massagué J (1986) The antiproliferative effect of type β transforming growth factor occurs at a level distal from receptors for growth activating factors. J. Biol. Chem. 261: 13426–13429.Google Scholar
  40. 40.
    Markovac J and Goldstein GW (1988) Transforming growth: factor beta activates protein kinase C in microvessels isolated from immature rat brain. Biochem. Biophys. Res. Comm. 150: 575–582.Google Scholar
  41. 41.
    Massagué J and Like B (1985) Cellular receptors for type β transforming growth factor. Ligand binding and affinity labeling in human and rodent cell lines. J. Biol. Chem. 260: 2636–2645.Google Scholar
  42. 42.
    Massagué J (1985a) Subunit structure of a high affinity receptor for type β-transforming growth factor. Evidence for a disulfide-linked glycosylated receptor complex. J. Biol. Chem. 260: 7059–7066.Google Scholar
  43. 43.
    Massagué J (1985b) Type-β transforming growth factor receptors in cells chronically exposed to the ligand. In: Feramisco J, Ozanne B and Stiles C (eds.) Cancer Cells 3: Growth Factors and Transformation (pp. 73–78) Cold Spring Harbor, New York.Google Scholar
  44. 44.
    Massagué J, Cheifetz S, Endo T and Nadai-Ginard B (1986) Type β transforming growth factor is an inhibitor of myogenic differentiation. Proc. Natl. Acad. Sci. USA 83: 8206–8210.Google Scholar
  45. 45.
    Massagué J and Kelly B (1986) Internalization of transforming growth factor-β and its receptor in BALB/c 3T3 fibroblasts. J. Cll. Phys. 128: 216–222.Google Scholar
  46. 46.
    Muldoon LL, Rodland KD and Magun BE (1988) Transforming growth factor β modulates epidermal factor-induced phosphoinositide metabolism and intracellular calcium levels. J. Biol. Chem. 263: 5030–5033.Google Scholar
  47. 47.
    Müller GA, Behrens J, Nussbaumer U, Böhlen P and Birchmeier W (1987) Inhibitory action of transforming growth factor-β on endothelial cells. Proc. Natl. Acad. Sci. USA 84: 5600–5604.Google Scholar
  48. 48.
    Ohta M, Greenberger JS, Anklesaria P, Bassels A and Massagué J (1987) Two forms of transforming growth factor-β distinguished by multipotential haemopoietic progenitor cells. Nature 329: 539–541.Google Scholar
  49. 49.
    Olson EN, Sternberg E, Hu JS, Spizz G and Wilcox C (1986) Regulation of myogenic differentiation by type β transforming growth factor. J. Cell Biol. 103: 1799–1805.Google Scholar
  50. 50.
    Ottman OG and Pelus LM (1988) Differential proliferative effects of transforming growth factor-β on human hematopoietic progenitor cells. J. Immunol. 140: 2662–2665.Google Scholar
  51. 51.
    Overall CM, Wrana JL and Sodek J (1989) Independent regulation of collagenase, 72-kDa progelatinase, and metalloendoproteinase inhibitor expression in human fibroblasts by transforming growth factor-β. J. Biol. Chem. 264: 1860–1869.Google Scholar
  52. 52.
    Penttinen RP, Kobayashi S and Bornstein P (1988) Transforming growth factor β increases mRNA for matrix proteins both in the presence and in the absence of changes in mRNA stability. Proc. Natl. Acad. Sci. USA 85: 1105–1108.Google Scholar
  53. 53.
    Raghow R, Postlethwaite AE, Keski-Oja J, Moses HL, Kang AH (1987) Transforming growth factor-β increases steady state levels of type I procollagen and fibronectin messenger mRNAs posttranscriptionally in cultured human dermal fibroblasts. J. Clin. Invest. 79: 1285–1288.Google Scholar
  54. 54.
    Rapraeger A, Koda JE and Bernfield M (1987) Matrix interactions of cell surface proteoglycans. In: Uitto J and Perejda A (eds.) Connective tissue disease: Molecular pathology of the extracellular matrix, pp. 213–231. M. Dekker, Inc. N. Y.Google Scholar
  55. 55.
    Rizzino A (1987) Appearance of high affinity receptors for type β transforming growth factor during differentiation of murine embryonal carcinoma cells. Canc. Res. 47: 4386–4390.Google Scholar
  56. 56.
    Rizzino A, Kazakoff P, Ruff E, Kuszynski C and Nebelsick J (1988) Regulatory effects of cell density on the binding of transforming growth factor β. epidermal growth factor, platelet-derived growth factor, and fibroblast growth factor. Canc. Res. 48: 4266–4271.Google Scholar
  57. 57.
    Roberts AB, Anzano MA, Lamb LC, Smith JM and Sporn MB (1981) New class of transforming growth factors potentiated by epidermal growth factor: Isolation from non-neoplastic tissues. Proc. Natl. Acad. Sci. USA 78: 5339–5343.Google Scholar
  58. 58.
    Roberts AB, Sporn MB, Assoian RF, Smith JM, Roche NS, Wakefield LM, Heine UI, Liotta LA, Falanga V, Kehrl JH and Fauci AS (1986) Transforming growth factor type β: Rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc. Natl. Acad. Sci. USA 83: 4167–4171.Google Scholar
  59. 59.
    Roberts CJ, Birkenmeier TM, McQuillan JJ, Akiyama SK, Yamada SS, Chen W-T, Yamada KM and McDonald JA (1988) Transforming growth factor β stimulates the expression of fibronectin and of both subunits of the human fibronectin receptor by cultural human lung fibroblasts. J. Biol. Chem. 263: 4586–4592.Google Scholar
  60. 60.
    Rosen DM, Stempien SA, Thompson AY and Seyedin SM (1988) Transforming growth factor-beta modulates the expression of osteoblast and chondroblast phenotypes in vitro. J. Cell Phys. 134: 337–346.Google Scholar
  61. 61.
    Segarini PR, Roberts AB, Rosen DM and Seyedin SM (1987) Membrane binding characteristics of two forms of transforming growth factor-β. J. Biol. Chem. 262: 14655–14662.Google Scholar
  62. 62.
    Segarini PR and Seyedin SM (1988) The high molecular weight receptor to transforming growth factor-β contains glycosaminoglycan chains. J. Biol. Chem. 263: 8366–8370.Google Scholar
  63. 63.
    Segarini PR, Rosen DM and Seyedin SM (1989) Binding of transforming growth factor-β to cell surface proteins varies with cell type. Mol. Endocrinol. 3: 261–272.Google Scholar
  64. 64.
    Seyedin SM, Thomas TC, Thompson AY, Rosen DM and Piez KP (1985) Purification and characterization of two-cartilage-inducing factors from bovine demineralized bone. Prog. Natl. Acad. Sci. USA 82: 2267–2271.Google Scholar
  65. 65.
    Silberstein GB and Daniel CW (1987) Reversible inhibition of mammary gland growth by transforming growth factor-β. Science 237: 291–293.Google Scholar
  66. 66.
    Sporn MB, Roberts AB, Wakefield LM and de Crombrugghe B (1987) Some recent advances in the chemistry and biology of transforming growth factor-Beta. J. Cell Biol. 105: 1039–1045.Google Scholar
  67. 67.
    ten Dijke P, Hansen P, Iwata KK, Pieler C, Foulkes JG (1988) Identification of another member of the transforming growth factor type β gene family. Proc. Natl. Acad. Sci. USA 85: 4715–4719.Google Scholar
  68. 68.
    Thompson NL, Flanders KC, Smith JM, Ellingsworth LR, Roberts AB and Sporn MB (1989) Expression of transforming growth factor-β1 in specific cells and tissue of adult and neonatal mice. J. Cell Biol. 108: 661–669.Google Scholar
  69. 69.
    Tucker RF, Branum EL, Shipley GD, Ryan RJ and Moses HL (1984) Specific binding of cultured cells of 125I-labeled type β transforming growth factor from human platelets. Proc. Nalt. Acad. Sci. USA 81: 6757–6761.Google Scholar
  70. 70.
    Wakefield IM, Smith DM, Masui T, Harris CC, Sporn MB (1987) Distribution and modulation of the cellular receptor for transforming growth factor-beta. J. Cell Biol. 105: 965–975.Google Scholar

Copyright information

© Kluwer Academic Publishers 1989

Authors and Affiliations

  • Patricia R. Segarini
    • 1
  1. 1.Celtrix LaboratoriesCollagen CorporationPalo AltoUSA

Personalised recommendations