| First Author | Wu J | Year | 2013 |
| Journal | Biochemistry | Volume | 52 |
| Issue | 50 | Pages | 9059-67 |
| PubMed ID | 24266852 | Mgi Jnum | J:209307 |
| Mgi Id | MGI:5566945 | Doi | 10.1021/bi4011804 |
| Citation | Wu J, et al. (2013) 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 |
| abstractText | 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 alpha-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 alpha-subunit of Na(+)/K(+)-ATPase with the SH3 domain of the p85 subunit of PI3K1A. |
