Figure 4.
Agonist-mediated GRK5 translocation to the nucleus. A: catecholamine or angiotensin II-mediated receptor activation leads to calmodulin activation through Gq. Calmodulin binds to the NH2 terminus of GRK5 dislodging from the plasma membrane and promoting nuclear localization. Nuclear GRK5 interaction to calmodulin is then stabilized by IP3-regulated calcium release. Nuclear GRK5 can act as an HDAC5 kinase, de-repressing MEF2 and inducing hypertrophic gene transcription. On the other hand, endothelin-1 receptor activation leads to its desensitization via GRK5 which cannot interact with calmodulin thus preventing nuclear translocation. B: cardiomyocytes from control rats (left column) and spontaneously hypertensive heart failure rats (SHHF) (right column). Myocytes are shown at different ages which correspond to: 2 (first row), 6 (second row), 12 (third row), and 24 mo old (fourth row). Confocal images labeling for GRK5 reveal a redistribution of GRK5 to the nucleus in SHHF rats. Scale bar equals 50 μm. [Image from studies of Yi et al. (281), with permission from John Wiley and Sons, Inc.]