Calcium Signalling in Heart and Vessels: Role of Calmodulin and Downstream Calmodulin-Dependent Protein Kinases

Figures

• 

  Figure 1. Schematic representation of Ca2+-CaM activation. After binding 4 ions of Ca2+, calmodulin undergoes conformational change that leads to activation of downstream proteins.

• 

  Figure 2. The 3D illustrations show the flexibility of calmodulin in binding to 4 Ca2+ and undergoing conformational changes for its reaction with a specific downstream protein, such as the CaM kinase proteins. Specifically, the binding of the calcium–calmodulin complex to auto-inhibitory target protein regions leads this conformational change and the target protein activation. Ca2+ is displayed as yellow balls and peptide is shown as magenta ribbon.

• 

  Figure 3. The general structure shared by the CaM-kinases. The N-terminal catalytic domain is represented in light blue, followed by a regulatory region containing in white the autoinhibitory domain and in dark blue the CaM-binding domain. The black block shows the C-terminal association domain of CaMKII. Adapted from Beghi S, et al., 2020 [39].

• 

  Figure 4. Ca2+-CaM kinases downstream of calmodulin. Binding of calcium to calmodulin leads to activation of the Ca2+-CaM-dependent kinase cascade, consisting of CaMKK1 and CaMKK2, CaMKI, and CaMKIV, as well as activation of CaMKII. The activation of CaMKKs regulates crucial cellular functions. Calcium calmodulin mediates downstream signalling of CaMKI, CaMKIV, AMPK, Akt, and mTOR.