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J Cell Biol. Aug 1, 1987; 105(2): 965–975.
PMCID: PMC2114751

Distribution and modulation of the cellular receptor for transforming growth factor-beta

Abstract

Scatchard analyses of the binding of transforming growth factor-beta (TGF-beta) to a wide variety of different cell types in culture revealed the universal presence of high affinity (Kd = 1-60 pM) receptors for TGF-beta on every cell type assayed, indicating a wide potential target range for TGF-beta action. There was a strong (r = +0.85) inverse relationship between the receptor affinity and the number of receptors expressed per cell, such that at low TGF-beta concentrations, essentially all cells bound a similar number of TGF- beta molecules per cell. The binding of TGF-beta to various cell types was not altered by many agents that affect the cellular response to TGF- beta, suggesting that modulation of TGF-beta binding to its receptor may not be a primary control mechanism in TGF-beta action. Similarly, in vitro transformation resulted in only relatively small changes in the cellular binding of TGF-beta, and for those cell types that exhibited ligand-induced down-regulation of the receptor, down- regulation was not extensive. Thus the strong conservation of binding observed between cell types is also seen within a given cell type under a variety of conditions, and receptor expression appears to be essentially constitutive. Finally, the biologically inactive form of TGF-beta, which constitutes greater than 98% of autocrine TGF-beta secreted by all of the twelve different cell types assayed, was shown to be unable to bind to the receptor without prior activation in vitro. It is proposed that this may prevent premature interaction of autocrine ligand and receptor in the Golgi apparatus.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Aharonov A, Pruss RM, Herschman HR. Epidermal growth factor. Relationship between receptor regulation and mitogenesis in 3T3 cells. J Biol Chem. 1978 Jun 10;253(11):3970–3977. [PubMed]
  • Anzano MA, Roberts AB, De Larco JE, Wakefield LM, Assoian RK, Roche NS, Smith JM, Lazarus JE, Sporn MB. Increased secretion of type beta transforming growth factor accompanies viral transformation of cells. Mol Cell Biol. 1985 Jan;5(1):242–247. [PMC free article] [PubMed]
  • Assoian RK, Frolik CA, Roberts AB, Miller DM, Sporn MB. Transforming growth factor-beta controls receptor levels for epidermal growth factor in NRK fibroblasts. Cell. 1984 Jan;36(1):35–41. [PubMed]
  • Assoian RK, Grotendorst GR, Miller DM, Sporn MB. Cellular transformation by coordinated action of three peptide growth factors from human platelets. Nature. 309(5971):804–806. [PubMed]
  • Assoian RK, Komoriya A, Meyers CA, Miller DM, Sporn MB. Transforming growth factor-beta in human platelets. Identification of a major storage site, purification, and characterization. J Biol Chem. 1983 Jun 10;258(11):7155–7160. [PubMed]
  • Betsholtz C, Westermark B, Ek B, Heldin CH. Coexpression of a PDGF-like growth factor and PDGF receptors in a human osteosarcoma cell line: implications for autocrine receptor activation. Cell. 1984 Dec;39(3 Pt 2):447–457. [PubMed]
  • Bowen-Pope DF, Dicorleto PE, Ross R. Interactions between the receptors for platelet-derived growth factor and epidermal growth factor. J Cell Biol. 1983 Mar;96(3):679–683. [PMC free article] [PubMed]
  • Bowen-Pope DF, Vogel A, Ross R. Production of platelet-derived growth factor-like molecules and reduced expression of platelet-derived growth factor receptors accompany transformation by a wide spectrum of agents. Proc Natl Acad Sci U S A. 1984 Apr;81(8):2396–2400. [PMC free article] [PubMed]
  • Carpenter G, Cohen S. Epidermal growth factor. Annu Rev Biochem. 1979;48:193–216. [PubMed]
  • Carr BI, Hayashi I, Branum EL, Moses HL. Inhibition of DNA synthesis in rat hepatocytes by platelet-derived type beta transforming growth factor. Cancer Res. 1986 May;46(5):2330–2334. [PubMed]
  • Cheifetz S, Weatherbee JA, Tsang ML, Anderson JK, Mole JE, Lucas R, Massagué J. The transforming growth factor-beta system, a complex pattern of cross-reactive ligands and receptors. Cell. 1987 Feb 13;48(3):409–415. [PubMed]
  • 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. [PMC free article] [PubMed]
  • Derynck R, Jarrett JA, Chen EY, Goeddel DV. The murine transforming growth factor-beta precursor. J Biol Chem. 1986 Apr 5;261(10):4377–4379. [PubMed]
  • Fanger BO, Wakefield LM, Sporn MB. Structure and properties of the cellular receptor for transforming growth factor type beta. Biochemistry. 1986 Jun 3;25(11):3083–3091. [PubMed]
  • Florini JR, Roberts AB, Ewton DZ, Falen SL, Flanders KC, Sporn MB. Transforming growth factor-beta. A very potent inhibitor of myoblast differentiation, identical to the differentiation inhibitor secreted by Buffalo rat liver cells. J Biol Chem. 1986 Dec 15;261(35):16509–16513. [PubMed]
  • Frolik CA, Wakefield LM, Smith DM, Sporn MB. Characterization of a membrane receptor for transforming growth factor-beta in normal rat kidney fibroblasts. J Biol Chem. 1984 Sep 10;259(17):10995–11000. [PubMed]
  • Garrett JS, Coughlin SR, Niman HL, Tremble PM, Giels GM, Williams LT. Blockade of autocrine stimulation in simian sarcoma virus-transformed cells reverses down-regulation of platelet-derived growth factor receptors. Proc Natl Acad Sci U S A. 1984 Dec;81(23):7466–7470. [PMC free article] [PubMed]
  • Goding JW. Use of staphylococcal protein A as an immunological reagent. J Immunol Methods. 1978;20:241–253. [PubMed]
  • Huang JS, Huang SS, Deuel TF. Transforming protein of simian sarcoma virus stimulates autocrine growth of SSV-transformed cells through PDGF cell-surface receptors. Cell. 1984 Nov;39(1):79–87. [PubMed]
  • Ignotz RA, Massagué J. Type beta transforming growth factor controls the adipogenic differentiation of 3T3 fibroblasts. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8530–8534. [PMC free article] [PubMed]
  • Jetten AM. Action of retinoids and phorbol esters on cell growth and the binding of epidermal growth factor. Ann N Y Acad Sci. 1981 Feb 27;359:200–217. [PubMed]
  • Kehrl JH, Roberts AB, Wakefield LM, Jakowlew S, Sporn MB, Fauci AS. Transforming growth factor beta is an important immunomodulatory protein for human B lymphocytes. J Immunol. 1986 Dec 15;137(12):3855–3860. [PubMed]
  • Kehrl JH, Wakefield LM, Roberts AB, Jakowlew S, Alvarez-Mon M, Derynck R, Sporn MB, Fauci AS. Production of transforming growth factor beta by human T lymphocytes and its potential role in the regulation of T cell growth. J Exp Med. 1986 May 1;163(5):1037–1050. [PMC free article] [PubMed]
  • Kono T, Barham FW. The relationship between the insulin-binding capacity of fat cells and the cellular response to insulin. Studies with intact and trypsin-treated fat cells. J Biol Chem. 1971 Oct 25;246(20):6210–6216. [PubMed]
  • Krycève-Martinerie C, Lawrence DA, Crochet J, Jullien P, Vigier P. Further study of beta-TGFs released by virally transformed and non-transformed cells. Int J Cancer. 1985 Apr 15;35(4):553–558. [PubMed]
  • Lawrence DA, Pircher R, Krycève-Martinerie C, Jullien P. Normal embryo fibroblasts release transforming growth factors in a latent form. J Cell Physiol. 1984 Oct;121(1):184–188. [PubMed]
  • Lechner JF, Haugen A, Autrup H, McClendon IA, Trump BF, Harris CC. Clonal growth of epithelial cells from normal adult human bronchus. Cancer Res. 1981 Jun;41(6):2294–2304. [PubMed]
  • Lechner JF, Tokiwa T, LaVeck M, Benedict WF, Banks-Schlegel S, Yeager H, Jr, Banerjee A, Harris CC. Asbestos-associated chromosomal changes in human mesothelial cells. Proc Natl Acad Sci U S A. 1985 Jun;82(11):3884–3888. [PMC free article] [PubMed]
  • Lee LS, Weinstein IB. Tumor-promoting phorbol esters inhibit binding of epidermal growth factor to cellular receptors. Science. 1978 Oct 20;202(4365):313–315. [PubMed]
  • Massagué J, Kelly B. Internalization of transforming growth factor-beta and its receptor in BALB/c 3T3 fibroblasts. J Cell Physiol. 1986 Aug;128(2):216–222. [PubMed]
  • Masui T, Wakefield LM, Lechner JF, LaVeck MA, Sporn MB, Harris CC. Type beta transforming growth factor is the primary differentiation-inducing serum factor for normal human bronchial epithelial cells. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2438–2442. [PMC free article] [PubMed]
  • Pircher R, Lawrence DA, Jullien P. Latent beta-transforming growth factor in nontransformed and Kirsten sarcoma virus-transformed normal rat kidney cells, clone 49F. Cancer Res. 1984 Dec;44(12 Pt 1):5538–5543. [PubMed]
  • Roberts AB, Anzano MA, Lamb LC, Smith JM, Sporn MB. Antagonistic actions of retinoic acid and dexamethasone on anchorage-independent growth and epidermal growth factor binding of normal rat kidney cells. Cancer Res. 1984 Apr;44(4):1635–1641. [PubMed]
  • Roberts AB, Anzano MA, Wakefield LM, Roche NS, Stern DF, Sporn MB. Type beta transforming growth factor: a bifunctional regulator of cellular growth. Proc Natl Acad Sci U S A. 1985 Jan;82(1):119–123. [PMC free article] [PubMed]
  • Roberts AB, Frolik CA, Anzano MA, Sporn MB. Transforming growth factors from neoplastic and nonneoplastic tissues. Fed Proc. 1983 Jun;42(9):2621–2626. [PubMed]
  • Roberts AB, Roche NS, Sporn MB. Selective inhibition of the anchorage-independent growth of myc-transfected fibroblasts by retinoic acid. Nature. 1985 May 16;315(6016):237–239. [PubMed]
  • Roberts AB, Sporn MB. Transforming growth factors. Cancer Surv. 1985;4(4):683–705. [PubMed]
  • Rook AH, Kehrl JH, Wakefield LM, Roberts AB, Sporn MB, Burlington DB, Lane HC, Fauci AS. Effects of transforming growth factor beta on the functions of natural killer cells: depressed cytolytic activity and blunting of interferon responsiveness. J Immunol. 1986 May 15;136(10):3916–3920. [PubMed]
  • Rozengurt E, Collins M, Brown KD, Pettican P. Inhibition of epidermal growth factor binding to mouse cultured cells by fibroblast-derived growth factor. Evidence for an indirect mechanism. J Biol Chem. 1982 Apr 10;257(7):3680–3686. [PubMed]
  • Schwartz SM. Selection and characterization of bovine aortic endothelial cells. In Vitro. 1978 Dec;14(12):966–980. [PubMed]
  • Seyedin SM, Thompson AY, Bentz H, Rosen DM, McPherson JM, Conti A, Siegel NR, Galluppi GR, Piez KA. Cartilage-inducing factor-A. Apparent identity to transforming growth factor-beta. J Biol Chem. 1986 May 5;261(13):5693–5695. [PubMed]
  • Shipley GD, Pittelkow MR, Wille JJ, Jr, Scott RE, Moses HL. Reversible inhibition of normal human prokeratinocyte proliferation by type beta transforming growth factor-growth inhibitor in serum-free medium. Cancer Res. 1986 Apr;46(4 Pt 2):2068–2071. [PubMed]
  • Sporn MB, Roberts AB. Autocrine growth factors and cancer. Nature. 313(6005):745–747. [PubMed]
  • Sporn MB, Roberts AB, Wakefield LM, Assoian RK. Transforming growth factor-beta: biological function and chemical structure. Science. 1986 Aug 1;233(4763):532–534. [PubMed]
  • Sporn MB, Todaro GJ. Autocrine secretion and malignant transformation of cells. N Engl J Med. 1980 Oct 9;303(15):878–880. [PubMed]
  • Todaro GJ, De Larco JE, Cohen S. Transformation by murine and feline sarcoma viruses specifically blocks binding of epidermal growth factor to cells. Nature. 1976 Nov 4;264(5581):26–31. [PubMed]
  • Tucker RF, Branum EL, Shipley GD, Ryan RJ, Moses HL. Specific binding to cultured cells of 125I-labeled type beta transforming growth factor from human platelets. Proc Natl Acad Sci U S A. 1984 Nov;81(21):6757–6761. [PMC free article] [PubMed]
  • Tucker RF, Shipley GD, Moses HL, Holley RW. Growth inhibitor from BSC-1 cells closely related to platelet type beta transforming growth factor. Science. 1984 Nov 9;226(4675):705–707. [PubMed]

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