Phosphorylation of Ser-446 Determines Stability of MKP-7
In: Journal of Biological Chemistry, Jg. 280 (2005-04-01), S. 14716-14722
Online
unknown
Zugriff:
MAPK cascades can be negatively regulated by members of the MAPK phosphatase (MKP) family. However, how MKP activity is regulated is not well characterized. MKP-7, a JNK-specific phosphatase, possesses a unique COOH-terminal stretch (CTS) in addition to domains conserved among MKP family members. The CTS contains several motifs such as a nuclear localization signal, a nuclear export signal, PEST sequences, and a serine residue (Ser-446) that can be phosphorylated by activated ERK, suggesting an important regulatory role(s).(35)S-pulse labeling experiments indicate that the half-life of MKP-7 is 1.5 h, a period significantly elongated by deleting the CTS. We also show that overexpressed MKP-7 is polyubiquitinated when co-expressed with ubiquitin and that proteasome inhibitors markedly inhibit MKP-7 degradation. We also determined that MKP-7 phosphorylated at Ser-446 has a longer half-life than unphosphorylated form of the wild type protein, as does a phospho-mimic mutant of MKP-7. These results indicate that activation of the ERK pathway strongly blocks JNK activation through stabilization of MKP-7 mediated by phosphorylation.
Titel: |
Phosphorylation of Ser-446 Determines Stability of MKP-7
|
---|---|
Autor/in / Beteiligte Person: | Shima, Hiroshi ; Araki, Yoshio ; Urano, Takeshi ; Masuda, Kouhei ; Katagiri, Chiaki ; Yamashita, Katsumi ; Kikuchi, Kunimi |
Link: | |
Zeitschrift: | Journal of Biological Chemistry, Jg. 280 (2005-04-01), S. 14716-14722 |
Veröffentlichung: | Elsevier BV, 2005 |
Medientyp: | unknown |
ISSN: | 0021-9258 (print) |
DOI: | 10.1074/jbc.m500200200 |
Schlagwort: |
|
Sonstiges: |
|