Posttranslational proteolytic processing of Leda-1/Pianp involves cleavage by MMPs, ADAM10/17 and gamma-secretase
Leda-1/Pianp is a type I transmembrane protein expressed by CNS cells, murine melanoma cell line B16F10 and rat liver sinusoidal endothelial cells. The early steps of posttranslational modifications of Leda-1/Pianp have been described to include glycosylation and processing by proprotein convertases...
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| Main Authors: | , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2 September 2016
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| In: |
Biochemical and biophysical research communications
Year: 2016, Volume: 477, Issue: 4, Pages: 661-666 |
| ISSN: | 1090-2104 |
| DOI: | 10.1016/j.bbrc.2016.06.116 |
| Online Access: | Verlag, Volltext: https://doi.org/10.1016/j.bbrc.2016.06.116 Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S0006291X16310348 
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| Author Notes: | Siladitta Biswas, Monica Adrian, Jochen Weber, Konstantin Evdokimov, Manuel Winkler, Cyrill Géraud |
| Summary: | Leda-1/Pianp is a type I transmembrane protein expressed by CNS cells, murine melanoma cell line B16F10 and rat liver sinusoidal endothelial cells. The early steps of posttranslational modifications of Leda-1/Pianp have been described to include glycosylation and processing by proprotein convertases. Here, we comprehensively characterized the subsequent steps of proteolytic processing of Leda-1/Pianp. For this purpose specific protease inhibitors and cell lines deficient in PS1, PS2, PS1/PS2 and ADAM10/17 were deployed. Leda-1/Pianp was cleaved at numerous cleavage sites within the N-terminal extracellular domain. The sheddases involved included MMPs and ADAM10/17. Ectodomain shedding yielded C-terminal fragments (CTF) of ∼15 kDa. The CTF was further processed by the γ (gamma)-secretase complex to generate the intracellular domain (ICD) of ∼10 kDa. Although PS1 was the dominant intramembrane protease, PS2 was also able to cleave Leda-1/Pianp in the absence of PS1. Thus, Leda-1/Pianp is constitutively processed by proprotein convertases, sheddases including MMPs and ADAM10/17 and intramembrane protease γ-secretase. |
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| Item Description: | Gesehen am 31.07.2019 Available online 24 June 2016 |
| Physical Description: | Online Resource |
| ISSN: | 1090-2104 |
| DOI: | 10.1016/j.bbrc.2016.06.116 |