The sodium-hydrogen exchanger NHE1 is an Akt substrate necessary for actin filament reorganization by growth factors.
J Biol Chem
; 284(39): 26666-75, 2009 Sep 25.
Article
em En
| MEDLINE
| ID: mdl-19622752
ABSTRACT
The kinase Akt mediates signals from growth factor receptors for increased cell proliferation, survival, and migration, which contribute to the positive effects of Akt in cancer progression. Substrates are generally inhibited when phosphorylated by Akt; however, we show phosphorylation of the plasma membrane sodium-hydrogen exchanger NHE1 by Akt increases exchanger activity (H(+) efflux). Our data fulfill criteria for NHE1 being a bona fide Akt substrate, including direct phosphorylation in vitro, using mass spectrometry and Akt phospho-substrate antibodies to identify Ser(648) as the Akt phosphorylation site and loss of increased exchanger phosphorylation and activity by insulin and platelet-derived growth factor in fibroblasts expressing a mutant NHE1-S648A. How Akt induces actin cytoskeleton remodeling to promote cell migration and tumor cell metastasis is unclear, but disassembly of actin stress fibers by platelet-derived growth factor and insulin and increased proliferation in growth medium are inhibited in fibroblasts expressing NHE1-S648A. We predict that other functions shared by Akt and NHE1, including cell growth and survival, might be regulated by increased H(+) efflux.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Actinas
/
Trocadores de Sódio-Hidrogênio
/
Peptídeos e Proteínas de Sinalização Intercelular
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Proteínas Proto-Oncogênicas c-akt
/
Fibroblastos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article