Figure 7. Proposed Mechanism of Hsp20 Regulating Cardiac Contractility.
The intricate balance between protein kinase and phosphatase activities regulates the phosphorylation of phospholamban in cardiomyocytes. Dephosphorylated PLN poses an inhibitory effect on the activity of SERCA. Dephosphorylation of PLN is mainly mediated by PP1. PKA- and CaMKII-dependent phosphorylation of PLN at Ser16 and Thr17, respectively, relieves PLN inhibition of SERCA and allows for increased Ca-pumping into the SR. Through inhibition of PP1 activity, overexpression of Hsp20 shifts the balance of kinase and PP1 activities, and favors enhanced phosphorylation of PLN and increased cardiac performance.