Latent TGF-β-binding proteins
- PMID: 25960419
- PMCID: PMC4844006
- DOI: 10.1016/j.matbio.2015.05.005
Latent TGF-β-binding proteins
Abstract
The LTBPs (or latent transforming growth factor β binding proteins) are important components of the extracellular matrix (ECM) that interact with fibrillin microfibrils and have a number of different roles in microfibril biology. There are four LTBPs isoforms in the human genome (LTBP-1, -2, -3, and -4), all of which appear to associate with fibrillin and the biology of each isoform is reviewed here. The LTBPs were first identified as forming latent complexes with TGFβ by covalently binding the TGFβ propeptide (LAP) via disulfide bonds in the endoplasmic reticulum. LAP in turn is cleaved from the mature TGFβ precursor in the trans-golgi network but LAP and TGFβ remain strongly bound through non-covalent interactions. LAP, TGFβ, and LTBP together form the large latent complex (LLC). LTBPs were originally thought to primarily play a role in maintaining TGFβ latency and targeting the latent growth factor to the extracellular matrix (ECM), but it has also been shown that LTBP-1 participates in TGFβ activation by integrins and may also regulate activation by proteases and other factors. LTBP-3 appears to have a role in skeletal formation including tooth development. As well as having important functions in TGFβ regulation, TGFβ-independent activities have recently been identified for LTBP-2 and LTBP-4 in stabilizing microfibril bundles and regulating elastic fiber assembly.
Keywords: Extracellular matrix; Latency associated protein; Latent TGFβ binding proteins; TGFβ activation.
Copyright © 2015. Published by Elsevier B.V.
Figures



Similar articles
-
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.
-
Assembly of fibrillin microfibrils governs extracellular deposition of latent TGF beta.J Cell Sci. 2010 Sep 1;123(Pt 17):3006-18. doi: 10.1242/jcs.073437. Epub 2010 Aug 10. J Cell Sci. 2010. PMID: 20699357 Free PMC article.
-
Specific sequence motif of 8-Cys repeats of TGF-beta binding proteins, LTBPs, creates a hydrophobic interaction surface for binding of small latent TGF-beta.Mol Biol Cell. 2000 Aug;11(8):2691-704. doi: 10.1091/mbc.11.8.2691. Mol Biol Cell. 2000. PMID: 10930463 Free PMC article.
-
Latent transforming growth factor beta-binding protein 1 interacts with fibrillin and is a microfibril-associated protein.J Biol Chem. 2003 Jan 24;278(4):2750-7. doi: 10.1074/jbc.M209256200. Epub 2002 Nov 11. J Biol Chem. 2003. PMID: 12429738
-
LTBPs in biology and medicine: LTBP diseases.Matrix Biol. 2018 Oct;71-72:90-99. doi: 10.1016/j.matbio.2017.11.014. Epub 2017 Dec 5. Matrix Biol. 2018. PMID: 29217273 Free PMC article. Review.
Cited by
-
Role of glycosylation in TGF-β signaling and epithelial-to-mesenchymal transition in cancer.Protein Cell. 2021 Feb;12(2):89-106. doi: 10.1007/s13238-020-00741-7. Epub 2020 Jun 25. Protein Cell. 2021. PMID: 32583064 Free PMC article. Review.
-
Function of Ltbp-4L and fibulin-4 in survival and elastogenesis in mice.Dis Model Mech. 2016 Nov 1;9(11):1367-1374. doi: 10.1242/dmm.026005. Epub 2016 Sep 1. Dis Model Mech. 2016. PMID: 27585882 Free PMC article.
-
Activation of latent transforming growth factor-β1, a conserved function for pregnancy-specific beta 1-glycoproteins.Mol Hum Reprod. 2018 Dec 1;24(12):602-612. doi: 10.1093/molehr/gay044. Mol Hum Reprod. 2018. PMID: 30371828 Free PMC article.
-
LncRNAs in TGF-β-Driven Tissue Fibrosis.Noncoding RNA. 2018 Oct 4;4(4):26. doi: 10.3390/ncrna4040026. Noncoding RNA. 2018. PMID: 30287731 Free PMC article. Review.
-
Matrix modeling and remodeling: A biological interplay regulating tissue homeostasis and diseases.Matrix Biol. 2019 Jan;75-76:1-11. doi: 10.1016/j.matbio.2018.08.007. Epub 2018 Aug 18. Matrix Biol. 2019. PMID: 30130584 Free PMC article. Review.
References
-
- Ali M, McKibbin M, Booth A, Parry DA, Jain P, Riazuddin SA, Hejtmancik JF, Khan SN, Firasat S, Shires M, Gilmour DF, Towns K, Murphy A-L, Azmanov D, Tournev I, Cherninkova S, Jafri H, Raashid Y, Toomes C, Craig J, Mackey DA, Kalaydjieva L, Riazuddin S, Inglehearn CF. Null mutations in LTBP2 cause primary congenital glaucoma. Am J Hum Genet. 2009;84(5):664–671. - PMC - PubMed
-
- Anderson SB, Goldberg AL, Whitman M. Identification of a novel pool of extracellular promyostatin in skeletal muscle. The Journal of biological chemistry. 2008;283(11):7027–7035. - PubMed
-
- Bai Y, Zhang P, Zhang X, Huang J, Hu S, Wei Y. LTBP-2 acts as a novel marker in human heart failure - a preliminary study. Biomarkers. 2012;17(5):407–415. - PubMed
-
- Bellusci S, Henderson R, Winnier G, Oikawa T, Hogan BL. Evidence from normal expression and targeted misexpression that bone morphogenetic protein (Bmp-4) plays a role in mouse embryonic lung morphogenesis. Development. 1996;122(6):1693–1702. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous