Identification of in vivo phosphorylation sites and their functional significance in the sodium iodide symporter.
J Biol Chem
; 282(51): 36820-8, 2007 Dec 21.
Article
em En
| MEDLINE
| ID: mdl-17913707
ABSTRACT
The Na+/I- symporter (NIS)-mediated iodide uptake activity is the basis for targeted radioiodide ablation of thyroid cancers. Although it has been shown that NIS protein is phosphorylated, neither the in vivo phosphorylation sites nor their functional significance has been reported. In this study, Ser-43, Thr-49, Ser-227, Thr-577, and Ser-581 were identified as in vivo NIS phosphorylation sites by mass spectrometry. Kinetic analysis of NIS mutants of the corresponding phosphorylated amino acid residue indicated that the velocity of iodide transport of NIS is modulated by the phosphorylation status of Ser-43 and Ser-581. We also found that the phosphorylation status of Thr-577 may be important for NIS protein stability and that the phosphorylation status of Ser-227 is functionally silent. Thr-49 appears to be critical for proper local structure/conformation of NIS because mutation of Thr-49 to alanine, aspartic acid, or serine results in reduced NIS activity without alterations in total or cell surface NIS protein levels. Taken together, we showed that NIS protein levels and functional activity could be modulated by phosphorylation through distinct mechanisms.
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Base de dados:
MEDLINE
Assunto principal:
Processamento de Proteína Pós-Traducional
/
Simportadores
/
Iodetos
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article