| Autor: |
Wang JY; Department of Biology, Emory University, Atlanta, Georgia 30322, USA., Miller SJ, Falls DL |
| Jazyk: |
angličtina |
| Zdroj: |
The Journal of biological chemistry [J Biol Chem] 2001 Jan 26; Vol. 276 (4), pp. 2841-51. Date of Electronic Publication: 2000 Oct 20. |
| DOI: |
10.1074/jbc.M005700200 |
| Abstrakt: |
Two neuregulin-1 isoforms highly expressed in the nervous system are the type III neuregulin III-beta1a and the type I neuregulin I-beta1a. The sequence of these two isoforms differs only in the region that is N-terminal of the bioactive epidermal growth factor-like domain. While the biosynthetic processing of the I-beta1a isoform has been well characterized, the processing of III-beta1a has not been reported. In this study, we compared III-beta1a and I-beta1a processing. Both III-beta1a and I-beta1a were synthesized as transmembrane proproteins that were proteolytically cleaved to produce an N-terminal fragment containing the bioactive epidermal growth factor-like domain. For I-beta1a, this product was released into the medium. However, for III-beta1a, this product was a transmembrane protein. In cultures of cells expressing III-beta1a, the amount of neuregulin at the cell surface was much greater, and the amount in the medium was much less than in cultures expressing I-beta1a. Phorbol ester treatment and truncation of the cytoplasmic tail had markedly different effects on III-beta1a and I-beta1a processing. These results demonstrate an important role for the N-terminal region in determining neuregulin biosynthetic processing and show that a major product of III-beta1a processing is a tethered ligand that may act as a cell surface signaling molecule. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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