A role of the latent TGF-beta 1-binding protein in the assembly and secretion of TGF-beta 1
- PMID: 2022183
- PMCID: PMC452762
- DOI: 10.1002/j.1460-2075.1991.tb08049.x
A role of the latent TGF-beta 1-binding protein in the assembly and secretion of TGF-beta 1
Abstract
Transforming growth factor-beta 1 (TGF-beta 1) is synthesized as latent complexes with high molecular weights. The large latent complex of TGF-beta 1 in platelets is composed of three components, i.e. the mature TGF-beta 1, which is non-covalently associated with a disulphide-bonded complex of the N-terminal remnant of the TGF-beta 1 precursor (TGF-beta 1-latency associated peptide) and the latent TGF-beta 1 binding protein (LTBP). The TGF-beta 1-latency associated peptide is sufficient for the latency of TGF-beta 1, whereas the functions of LTBP remain to be elucidated. In a human erythroleukemia cell line, HEL, the production of the latent form of TGF-beta 1 was induced more than 100-fold by phorbol 12-myristate 13-acetate. Analysis by Northern blotting revealed that both the TGF-beta 1 precursor and LTBP were induced in a coordinated fashion. Analysis by immunoprecipitation using antibodies against LTBP and the TGF-beta 1 precursor dimer revealed that LTBP has a molecular size of 205 kd under reducing conditions in this cell type, i.e. similar to that from cells transfected with cDNA for LTBP, but larger than the platelet form (125-160 kd). Limited tryptic digestion of LTBP in HEL cells and analysis by SDS-PAGE showed protein bands of similar sizes to those of platelet LTBP, suggesting that the difference in molecular sizes of LTBP involves cell-specific processing. The biosynthesis of the latent TGF-beta 1 was studied by pulse-chase analysis. LTBP became covalently associated with the TGF-beta 1 precursor within 15 min after synthesis in this cell line. Secretion of the large latent TGF-beta 1 complex was observed as early as 30 min after the synthesis of LTBP; at the same time, a free form of LTBP not bound to the TGF-beta 1 precursor was seen. In contrast, the TGF-beta 1 precursor remained inside the cells in an unprocessed form for a longer time period and the TGF-beta 1 precursor dimer without LTBP was secreted only very slowly. Furthermore, the results of partial tryptic digestion of this molecule suggested that it contained improper disulphide bonding. These results suggest that LTBP plays a critical role in the assembly and secretion of the latent TGF-beta 1.
Similar articles
-
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):5668-75. J Biol Chem. 1992. PMID: 1544940
-
Latent transforming growth factor-beta complex in Chinese hamster ovary cells contains the multifunctional cysteine-rich fibroblast growth factor receptor, also termed E-selectin-ligand or MG-160.Biochem J. 1997 Jun 1;324 ( Pt 2)(Pt 2):427-34. doi: 10.1042/bj3240427. Biochem J. 1997. PMID: 9182700 Free PMC article.
-
Expression of different isoforms of TGF-beta and the latent TGF-beta binding protein (LTBP) by rat Kupffer cells.J Hepatol. 1998 Dec;29(6):915-22. doi: 10.1016/s0168-8278(98)80119-0. J Hepatol. 1998. PMID: 9875638
-
Latent transforming growth factor-beta binding proteins (LTBPs)--structural extracellular matrix proteins for targeting TGF-beta action.Cytokine Growth Factor Rev. 1999 Jun;10(2):99-117. doi: 10.1016/s1359-6101(99)00010-6. Cytokine Growth Factor Rev. 1999. PMID: 10743502 Review.
-
Extracellular matrix-associated transforming growth factor-beta: role in cancer cell growth and invasion.Adv Cancer Res. 1998;75:87-134. doi: 10.1016/s0065-230x(08)60740-x. Adv Cancer Res. 1998. PMID: 9709808 Review.
Cited by
-
Liver portal fibrosis in dioxin receptor-null mice that overexpress the latent transforming growth factor-beta-binding protein-1.Int J Exp Pathol. 2004 Oct;85(5):295-302. doi: 10.1111/j.0959-9673.2004.00397.x. Int J Exp Pathol. 2004. PMID: 15379962 Free PMC article.
-
Mice lacking neutrophil elastase are resistant to bleomycin-induced pulmonary fibrosis.Am J Pathol. 2007 Jan;170(1):65-74. doi: 10.2353/ajpath.2007.060352. Am J Pathol. 2007. PMID: 17200183 Free PMC article.
-
Latent transforming growth factor beta-binding protein-3 and fibulin-1C interact with the extracellular domain of the heparin-binding EGF-like growth factor precursor.BMC Cell Biol. 2002;3:2. doi: 10.1186/1471-2121-3-2. Epub 2002 Jan 22. BMC Cell Biol. 2002. PMID: 11846885 Free PMC article.
-
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):4879-87. doi: 10.1128/MCB.20.13.4879-4887.2000. Mol Cell Biol. 2000. PMID: 10848613 Free PMC article.
-
Dental Pulp Stem Cells: Advances to Applications.Stem Cells Cloning. 2020 Feb 13;13:33-42. doi: 10.2147/SCCAA.S166759. eCollection 2020. Stem Cells Cloning. 2020. PMID: 32104005 Free PMC article. Review.
References
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases