Another study [13] found that, in the early stages of heart failure, when β1-AR is activated, it can cause the β2-AR downstream signal to be converted from Gs to Gi, and Gi is activated by the activity of G protein-coupled receptor kinase 2 (GRK2), which then causes β1-AR phosphorylation, as well as β-arrestin binding to form endocytosis, after which β1-AR endocytosis [13] inhibits the overactivation of β1-AA. The gene discussed is GRK2; the disease is heart failure.