Skip to main content
NCBI home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1989 Dec 1;109(6):3137–3145. doi: 10.1083/jcb.109.6.3137

Membrane-anchored and soluble forms of betaglycan, a polymorphic proteoglycan that binds transforming growth factor-beta

PMCID: PMC2115961  PMID: 2592419

Abstract

Transforming growth factors beta 1 and beta 2 bind with high affinity to the core protein of a 250-350-kD cell surface proteoglycan. This proteoglycan (formerly referred to as the type III TGF-beta receptor) coexists in many cells with the receptor implicated in TGF-beta signal transduction (type I TGF-beta receptor), but its function is not known. We report here that soluble TGF-beta-binding proteoglycans are released by several cell types into the culture media, and can be found in serum and extracellular matrices. As has been shown for the membrane-bound form, the soluble proteoglycans have a heterogeneous core protein of 100-120 kD that carries chondroitin sulfate and/or heparan sulfate glycosaminoglycan chains and a small amount of N-linked carbohydrate. The membrane-bound form of this proteoglycan is hydrophobic and associates with liposomes, whereas the soluble forms lack a membrane anchor and do not associate with liposomes. Differences in the electrophoretic migration of the soluble and membrane forms of this proteoglycan suggest additional structural differences in their core proteins and glycosaminoglycan chains. These soluble and membrane-bound proteoglycans, for which we propose the name "betaglycans," might play distinct roles in pericellular retention, delivery, or clearance of activated TGF-beta.

Full Text

The Full Text of this article is available as a PDF (1.5 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bassols A., Massagué J. Transforming growth factor beta regulates the expression and structure of extracellular matrix chondroitin/dermatan sulfate proteoglycans. J Biol Chem. 1988 Feb 25;263(6):3039–3045. [PubMed] [Google Scholar]
  2. Boyd F. T., Massagué J. Transforming growth factor-beta inhibition of epithelial cell proliferation linked to the expression of a 53-kDa membrane receptor. J Biol Chem. 1989 Feb 5;264(4):2272–2278. [PubMed] [Google Scholar]
  3. Carrington J. L., Roberts A. B., Flanders K. C., Roche N. S., Reddi A. H. Accumulation, localization, and compartmentation of transforming growth factor beta during endochondral bone development. J Cell Biol. 1988 Nov;107(5):1969–1975. doi: 10.1083/jcb.107.5.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cheifetz S., Andres J. L., Massagué J. The transforming growth factor-beta receptor type III is a membrane proteoglycan. Domain structure of the receptor. J Biol Chem. 1988 Nov 15;263(32):16984–16991. [PubMed] [Google Scholar]
  5. Cheifetz S., Bassols A., Stanley K., Ohta M., Greenberger J., Massagué J. Heterodimeric transforming growth factor beta. Biological properties and interaction with three types of cell surface receptors. J Biol Chem. 1988 Aug 5;263(22):10783–10789. [PubMed] [Google Scholar]
  6. Cheifetz S., Like B., Massagué J. Cellular distribution of type I and type II receptors for transforming growth factor-beta. J Biol Chem. 1986 Jul 25;261(21):9972–9978. [PubMed] [Google Scholar]
  7. Cheifetz S., Weatherbee J. A., Tsang M. L., Anderson J. K., Mole J. E., 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. doi: 10.1016/0092-8674(87)90192-9. [DOI] [PubMed] [Google Scholar]
  8. Fisher L. W., Termine J. D., Young M. F. Deduced protein sequence of bone small proteoglycan I (biglycan) shows homology with proteoglycan II (decorin) and several nonconnective tissue proteins in a variety of species. J Biol Chem. 1989 Mar 15;264(8):4571–4576. [PubMed] [Google Scholar]
  9. Giblin P., Ledbetter J. A., Kavathas P. A secreted form of the human lymphocyte cell surface molecule CD8 arises from alternative splicing. Proc Natl Acad Sci U S A. 1989 Feb;86(3):998–1002. doi: 10.1073/pnas.86.3.998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Goldstein L. A., Zhou D. F., Picker L. J., Minty C. N., Bargatze R. F., Ding J. F., Butcher E. C. A human lymphocyte homing receptor, the hermes antigen, is related to cartilage proteoglycan core and link proteins. Cell. 1989 Mar 24;56(6):1063–1072. doi: 10.1016/0092-8674(89)90639-9. [DOI] [PubMed] [Google Scholar]
  11. Gower H. J., Barton C. H., Elsom V. L., Thompson J., Moore S. E., Dickson G., Walsh F. S. Alternative splicing generates a secreted form of N-CAM in muscle and brain. Cell. 1988 Dec 23;55(6):955–964. doi: 10.1016/0092-8674(88)90241-3. [DOI] [PubMed] [Google Scholar]
  12. Hashimoto C., Hudson K. L., Anderson K. V. The Toll gene of Drosophila, required for dorsal-ventral embryonic polarity, appears to encode a transmembrane protein. Cell. 1988 Jan 29;52(2):269–279. doi: 10.1016/0092-8674(88)90516-8. [DOI] [PubMed] [Google Scholar]
  13. Hassell J. R., Kimura J. H., Hascall V. C. Proteoglycan core protein families. Annu Rev Biochem. 1986;55:539–567. doi: 10.1146/annurev.bi.55.070186.002543. [DOI] [PubMed] [Google Scholar]
  14. Heine U., Munoz E. F., Flanders K. C., Ellingsworth L. R., Lam H. Y., Thompson N. L., Roberts A. B., Sporn M. B. Role of transforming growth factor-beta in the development of the mouse embryo. J Cell Biol. 1987 Dec;105(6 Pt 2):2861–2876. doi: 10.1083/jcb.105.6.2861. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ignotz R. A., 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. [PubMed] [Google Scholar]
  16. Ignotz R. A., 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. doi: 10.1073/pnas.82.24.8530. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Koda J. E., Rapraeger A., Bernfield M. Heparan sulfate proteoglycans from mouse mammary epithelial cells. Cell surface proteoglycan as a receptor for interstitial collagens. J Biol Chem. 1985 Jul 5;260(13):8157–8162. [PubMed] [Google Scholar]
  18. Krusius T., Ruoslahti E. Primary structure of an extracellular matrix proteoglycan core protein deduced from cloned cDNA. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7683–7687. doi: 10.1073/pnas.83.20.7683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Low M. G. Glycosyl-phosphatidylinositol: a versatile anchor for cell surface proteins. FASEB J. 1989 Mar;3(5):1600–1608. doi: 10.1096/fasebj.3.5.2522071. [DOI] [PubMed] [Google Scholar]
  20. Massagué J., Cheifetz S., Endo T., Nadal-Ginard B. Type beta transforming growth factor is an inhibitor of myogenic differentiation. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8206–8210. doi: 10.1073/pnas.83.21.8206. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Miller J., Hatch J. A., Simonis S., Cullen S. E. Identification of the glycosaminoglycan-attachment site of mouse invariant-chain proteoglycan core protein by site-directed mutagenesis. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1359–1363. doi: 10.1073/pnas.85.5.1359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Ohta M., Greenberger J. S., Anklesaria P., Bassols A., Massagué J. Two forms of transforming growth factor-beta distinguished by multipotential haematopoietic progenitor cells. Nature. 1987 Oct 8;329(6139):539–541. doi: 10.1038/329539a0. [DOI] [PubMed] [Google Scholar]
  23. Roberts A. B., Sporn M. B., Assoian R. K., Smith J. M., Roche N. S., Wakefield L. M., Heine U. I., Liotta L. A., Falanga V., Kehrl J. H. 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. doi: 10.1073/pnas.83.12.4167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Schubert D., Schroeder R., LaCorbiere M., Saitoh T., Cole G. Amyloid beta protein precursor is possibly a heparan sulfate proteoglycan core protein. Science. 1988 Jul 8;241(4862):223–226. doi: 10.1126/science.2968652. [DOI] [PubMed] [Google Scholar]
  25. Segarini P. R., Seyedin S. M. The high molecular weight receptor to transforming growth factor-beta contains glycosaminoglycan chains. J Biol Chem. 1988 Jun 15;263(17):8366–8370. [PubMed] [Google Scholar]
  26. Seyedin S. M., Thomas T. C., Thompson A. Y., Rosen D. M., Piez K. A. Purification and characterization of two cartilage-inducing factors from bovine demineralized bone. Proc Natl Acad Sci U S A. 1985 Apr;82(8):2267–2271. doi: 10.1073/pnas.82.8.2267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Stamenkovic I., Amiot M., Pesando J. M., Seed B. A lymphocyte molecule implicated in lymph node homing is a member of the cartilage link protein family. Cell. 1989 Mar 24;56(6):1057–1062. doi: 10.1016/0092-8674(89)90638-7. [DOI] [PubMed] [Google Scholar]
  28. Stroynowski I., Soloski M., Low M. G., Hood L. A single gene encodes soluble and membrane-bound forms of the major histocompatibility Qa-2 antigen: anchoring of the product by a phospholipid tail. Cell. 1987 Aug 28;50(5):759–768. doi: 10.1016/0092-8674(87)90334-5. [DOI] [PubMed] [Google Scholar]
  29. Wakefield L. M., Smith D. M., Flanders K. C., Sporn M. B. 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. [PubMed] [Google Scholar]
  30. Weitzhandler M., Streeter H. B., Henzel W. J., Bernfield M. The cell surface proteoglycan of mouse mammary epithelial cells. The extracellular domain contains N terminus and a peptide sequence present in a conditioned medium proteoglycan. J Biol Chem. 1988 May 25;263(15):6949–6952. [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES