Latency-associated peptide of transforming growth factor-β1 is not subject to physiological mannose phosphorylation. J Biol Chem 2012 Mar 02;287(10):7526-34
Date
01/21/2012Pubmed ID
22262853Pubmed Central ID
PMC3293579DOI
10.1074/jbc.M111.308825Scopus ID
2-s2.0-84857750167 (requires institutional sign-in at Scopus site) 9 CitationsAbstract
Latent TGF-β1 was one of the first non-lysosomal glycoproteins reported to bear mannose 6-phosphate (Man-6-P) residues on its N-glycans. Prior studies have suggested that this sugar modification regulates the activation of latent TGF-β1 by allowing it to bind cell surface-localized Man-6-P receptors. Man-6-P has also been proposed as an anti-scarring therapy based on its ability to directly block the activation of latent TGF-β1. A complete understanding of the physiological relevance of latent TGF-β1 mannose phosphorylation, however, is still lacking. Here we investigate the degree of mannose phosphorylation on secreted latent TGF-β1 and examine its Man-6-P-dependent activation in primary human corneal stromal fibroblasts. Contrary to earlier reports, minimal to no Man-6-P modification was found on secreted and cell-associated latent TGF-β1 produced from multiple primary and transformed cell types. Results showed that the inability to detect Man-6-P residues was not due to masking by the latent TGF-β1-binding protein (LTBP). Moreover, the efficient processing of glycans on latent TGF-β1 to complex type structures was consistent with the lack of mannose phosphorylation during biosynthesis. We further demonstrated that the conversion of corneal stromal fibroblast to myofibroblasts, a well known TGF-β1-dependent process, was not altered by Man-6-P addition when latent forms of this growth factor were present. Collectively, these findings indicate that Man-6-P-dependent effects on latent TGF-β1 activation are not mediated by direct modification of its latency-associated peptide.
Author List
Barnes J, Warejcka D, Simpliciano J, Twining S, Steet RAuthor
Sally S. Twining PhD Assistant Dean, Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCHO Cells
Cornea
Cricetinae
Cricetulus
Fibroblasts
HeLa Cells
Humans
K562 Cells
Latent TGF-beta Binding Proteins
Mannose
Mannosephosphates
Phosphorylation
Transforming Growth Factor beta1
