Cell signaling associated with Na(+)/K(+)-ATPase: activation of phosphatidylinositide 3-kinase IA/Akt by ouabain is independent of Src.
Biochemistry
; 52(50): 9059-67, 2013 Dec 17.
Article
em En
| MEDLINE
| ID: mdl-24266852
ABSTRACT
Exposure of intact cells to selective inhibitors of Na(+)/K(+)-ATPase such as ouabain activates several growth-related cell signaling pathways. It has been suggested that the initial event of these pathways is the binding of ouabain to a preexisting complex of Src with Na(+)/K(+)-ATPase of the plasma membrane. The aim of this work was to evaluate the role of Src in the ouabain-induced activation of phosphatidylinositide 3-kinase 1A (PI3K1A) and its downstream consequences. When fibroblasts devoid of Src (SYF cells) and controls (Src(++) cells) were exposed to ouabain, PI3K1A, Akt, and proliferative growth were similarly stimulated in both cell lines. Ouabain-induced activation of Akt was not prevented by the Src inhibitor PP2. In contrast, ERK1/2 were not activated by ouabain in SYF cells but were stimulated in Src(++) cells; this was prevented by PP2. In isolated adult mouse cardiac myocytes, where ouabain induces hypertrophic growth, PP2 also did not prevent ouabain-induced activation of Akt and the resulting hypertrophy. Ouabain-induced increases in the levels of co-immunoprecipitation of the α-subunit of Na(+)/K(+)-ATPase with the p85 subunit of PI3K1A were noted in SYF cells, Src(++) cells, and adult cardiac myocytes. In conjunction with previous findings, the results presented here indicate that (a) if there is a preformed complex of Src and Na(+)/K(+)-ATPase, it is irrelevant to ouabain-induced activation of the PI3K1A/Akt pathway through Na(+)/K(+)-ATPase and (b) a more likely, but not established, mechanism of linkage of Na(+)/K(+)-ATPase to PI3K1A is the ouabain-induced interaction of a proline-rich domain of the α-subunit of Na(+)/K(+)-ATPase with the SH3 domain of the p85 subunit of PI3K1A.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ouabaína
/
Transdução de Sinais
/
ATPase Trocadora de Sódio-Potássio
/
Proteínas Proto-Oncogênicas c-akt
/
Classe Ia de Fosfatidilinositol 3-Quinase
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Biochemistry
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos