| First Author | Biswas S | Year | 2016 |
| Journal | Biochem Biophys Res Commun | Volume | 477 |
| Issue | 4 | Pages | 661-666 |
| PubMed ID | 27349870 | Mgi Jnum | J:238594 |
| Mgi Id | MGI:5823128 | Doi | 10.1016/j.bbrc.2016.06.116 |
| Citation | Biswas S, et al. (2016) Posttranslational proteolytic processing of Leda-1/Pianp involves cleavage by MMPs, ADAM10/17 and gamma-secretase. Biochem Biophys Res Commun 477(4):661-6 |
| abstractText | 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 approximately 15 kDa. The CTF was further processed by the gamma (gamma)-secretase complex to generate the intracellular domain (ICD) of approximately 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 gamma-secretase. |
