Figure 7.

Src kinase regulation mediated by Na,K-ATPase in normoxic and hypoxic conditions. Under normixic conditions, Aβ binding leads to the release of the kinase domain of Src from the complex with the nucleotide binding domain (NBD) of Na,K-ATPase. The release induces Src kinase autophosphorylation at Tyr416 (located in the interaction interface), leading to an increase in the activity. In hypoxia, glutathionylation of the cysteine residues of the Na,K-ATPase NBD domain [73] from the interaction interface (Figure 5) was demonstrated and led to disruption of the interaction between Src kinase and Na,K-ATPase [47]. As a result, the binding of Aβ under hypoxic conditions does not lead to the activation of Src kinase.