Figure 7.

Schematic illustration of the signaling interplay between GRK5 and MR as well as between GRK2 and GPER inside cardiac myocytes. GRK5, activated by the cardiac β₂AR via PLCβ-Ca²⁺-CaM signaling, translocates to the cytoplasm to phosphorylate the MR and inhibit its transcriptional activity as a result of the Aldo–MR complex’s cytoplasmic-nuclear shuttling blockade. GRK2, on the other hand, phosphorylates and desensitizes the agonist-activated GPER at the plasma membrane. Aldo: Aldosterone; CA: Catecholamine; P: Phosphorylation; pSer: Phosphorylated serine; PLC: Phospholipase C; PIP₂: Phosphatidylinositol 4,5-bisphosphate; DAG: Diacylglycerol; IP₃: Inositol 1,4,5-trisphosphate; CaM: Calmodulin; ERK: Extracellular signal-regulated kinase. See text for more details and for all other molecular acronyms’ descriptions. Solid arrows denote direct activation/action, dotted arrows multi-step activation or translocation, and ⊣ denotes inhibition.