Identification of ADAM10 as a major TNF sheddase in ADAM17-deficient fibroblasts |
| |
| Authors: | Renata M&#x yk-Kope&#x , Monika Bzowska, Krystyna Stali&#x ska, Tomasz Che&#x micki, Micha&#x Podkalicki, Jaros&#x aw Jucha, Katarzyna Kowalczyk, Pawe&#x Mak,Joanna Bereta |
| |
| Affiliation: | aDepartment of Cell Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, ul. Gronostajowa 7, 30-387 Kraków, Poland;bDepartment of Analytical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, ul. Gronostajowa 7, 30-387 Kraków, Poland |
| |
| Abstract: | ADAM17 (a disintegrin and metalloprotease)-deficient murine fibroblasts stably transfected with proTNF cDNA release significant amounts of biologically active soluble TNF. The enzyme responsible for this activity is a membrane protein that hydrolyzes the peptide bond Ala76:Val77 within proTNF. Its activity is inhibited by 1,10-phenantroline and GM6001, insusceptible to TIMP-2 (tissue inhibitor of metalloproteinases-2), and stimulated by ionomycin. These characteristics match ADAM10. The moderate silencing of ADAM10 by shRNA resulted in a significant inhibition of TNF shedding. There was no correlation between the level of ADAM10 expression and the presence of active ADAM17. Our results indicate that ADAM10 may function as the TNF sheddase in cells which lack ADAM17 activity. |
| |
| Keywords: | Ectodomain shedding ADAM10 ADAM17 TNF RNA interference |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
