Résumé
The insulin IGF-1-PI3K-Akt signaling pathway has been suggested to improve cardiac inotropism and increase ... handling through the effects of the protein kinase Akt. However, the underlying molecular mechanisms remain largely unknown. In this study, we provide evidence for an unanticipated regulatory function of Akt controlling L-type ... channel (LTCC) protein density. The pore-forming channel subunit ...α1 contains highly conserved PEST sequences (signals for rapid protein degradation), and in-frame deletion of these PEST sequences results in increased ...α1 protein levels. Our findings show that Akt-dependent phosphorylation of ...β2, the LTCC chaperone for ...α1, antagonizes ...α1 protein degradation by preventing ...α1 PEST sequence recognition, leading to increased LTCC density and the consequent modulation of ... channel function. This novel mechanism by which Akt modulates LTCC stability could profoundly influence cardiac myocyte ... entry, ... handling, and contractility. (ProQuest: ... denotes formulae/symbols omitted.)