Molecular determinants and feedback circuits regulating type 2 CRH receptor signal integration

► Intracellular signals and interactions with AKAP regulate CRH-R2β-ERK activation. ► CRH-R2β induces PKB/Akt activation via Gi/o-proteins-PI3-K activation. ► ERK phosphorylates β-arr1 and modulates its translocation to the plasma membrane. ► Inhibition of either PKA or ERK pathway accelerates CRH-R2β endocytosis. ► The Akt signaling is insensitive to changes in receptor endocytosis rate.