Latency-associated peptide of transforming growth factor-β1 is not subject to physiological mannose phosphorylation
| Autor: | Sally S. Twining, Debra J. Warejcka, Jarrod W. Barnes, Jennifer M. Simpliciano, Richard Steet |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Stromal cell
medicine.medical_treatment Mannose Glycobiology and Extracellular Matrices CHO Cells Biology Biochemistry Cornea Transforming Growth Factor beta1 chemistry.chemical_compound Cricetulus Cricetinae medicine Animals Humans Phosphorylation Receptor Molecular Biology chemistry.chemical_classification Mannosephosphates Growth factor Cell Biology Fibroblasts carbohydrates (lipids) Latent TGF-beta binding protein chemistry Latent TGF-beta Binding Proteins Glycoprotein K562 Cells Transforming growth factor HeLa Cells |
| Zdroj: | The Journal of biological chemistry. 287(10) |
| ISSN: | 1083-351X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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