ARRBSArginine-Rich RNA Binding Site
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To further verify the effect of AKT phosphorylation in the TSH-stimulated cholesterol conversion pathway, ARRB1/2-KD HepG2 cells along with HepG2-Cas9 cells were treated with the AKT activator SC79, which binds to the pleckstrin homology domain independent of GPCRs and ARRBs. SC79-bound AKT adopts a conformation favorable to phosphorylation by upstream protein kinases [24].
Few previous studies have focused on the regulation of cholesterol metabolism by ARRBs. In Chinese hamster ovary (CHO) cells, the oxidative state of cell surface cholesterol is one of the factors involved in endothelin receptor type A (ETA) internalization, which occurs via caveolae or clathrin-coated pits [25].
Deficiencies of ARRBs, especially ARRB1, led to a decreased cholesterol level in liver tissues and cells.
ARRBs were first discovered to function in GPCR desensitization [28].
In addition to cholesterol synthesis, the cholesterol conversion process was taken into account to explain the influence of ARRBs on cholesterol.
(c) Grayscale analysis of relative expression level of ARRBs, HMGCR, and CYP7A1 of arrb1/2-KO mice and wild-type littermates.
Based on their different binding affinities to ARRB isoforms, GPCRs can be divided into two classes.