Following ligand-promoted internalization the human type 2 vasopressin receptor (hV2R) is not recycled to the cell surface after removal of the agonist. A retention motif consisting of a serine triplet present in the cytoplasmic tail was previously found to require for retention, but serine 357, and threonines 359, 360 located upstream were not examined. Evidence is now presented that substitution of these amino acids did not change V2 internalization although it reduced the levels of arginine vasopressin (AVP)-induced phosphorylation as compared to the wild type (WT). Contrary to the WT hV2R, these mutant receptors were recycled to the cell surface after a 2 h incubation in the absence of AVP identifying these changed residues as additional members of the retention motif of the hV2R.
