Figure 7.

Internalization-triggering signals and internalization of the Ang II AT₁ receptors. Label a, mechanism of heterologous internalization initiated by PKA and PKC; b, mechanism of conventional homologous internalization initiated by an activated G proteins; c, mechanism of unconventional homologous internalization initiated by G protein-independent signals; d, β-arrestin-dependent internalization (binding of β-arrestins to a GPCR is essential); e, β-arrestin-independent internalization (binding of other non-β-arrestin molecules such as caveolin or GRK2 is essential). Here R*, dR*, and iR* means activated, desensitized, and internalized AT₁ receptors, respectively. In this illustration GRKs play an important role in both G protein-dependent conventional homologous internalization and G protein-independent unconventional homologous internalization. Other kinases may also be involved in the initiation of homologous internalizations of the AT₁ receptor. Transactivation of EGFR is not only independent of AT₁ receptor internalization but also independent of G protein activation.