Functional rescue of a defective angiotensin II AT1 receptor mutant by the Mas protooncogene

Regul Pept. 2007 Jun 7;141(1-3):159-67. doi: 10.1016/j.regpep.2006.12.030. Epub 2007 Jan 20.


Earlier studies with Mas protooncogene, a member of the G-protein-coupled receptor family, have proposed this gene to code for a functional AngII receptor, however further results did not confirm this assumption. In this work we investigated the hypothesis that a heterodimeration AT(1)/Mas could result in a functional interaction between both receptors. For this purpose, CHO or COS-7 cells were transfected with the wild-type AT(1) receptor, a non-functional AT(1) receptor double mutant (C18F-K20A) and Mas or with WT/Mas and C18F-K20A/Mas. Cells single-expressing Mas or C18F/K20A did not show any binding for AngII. The co-expression of the wild-type AT(1) receptor and Mas showed a binding profile similar to that observed for the wild-type AT(1) expressed alone. Surprisingly, the co-expression of the double mutant C18F/K20A and Mas evoked a total recovery of the binding affinity for AngII to a level similar to that obtained for the wild-type AT(1). Functional measurements using inositol phosphate and extracellular acidification rate assays also showed a clear recovery of activity for AngII on cells co-expressing the mutant C18F/K20A and Mas. In addition, immunofluorescence analysis localized the AT(1) receptor mainly at the plasma membrane and the mutant C18F-K20A exclusively inside the cells. However, the co-expression of C18F-K20A mutant with the Mas changed the distribution pattern of the mutant, with intense signals at the plasma membrane, comparable to those observed in cells expressing the wild-type AT(1) receptor. These results support the hypothesis that Mas is able to rescue binding and functionality of the defective C18F-K20A mutant by dimerization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Angiotensin II / metabolism
  • Animals
  • CHO Cells
  • COS Cells
  • Cell Membrane / metabolism
  • Chlorocebus aethiops
  • Cricetinae
  • Cricetulus
  • Fluoresceins
  • Fluorescent Antibody Technique, Direct
  • Fluorescent Dyes
  • Indoles
  • Inhibitory Concentration 50
  • Inositol Phosphates / analysis
  • Inositol Phosphates / metabolism
  • Models, Chemical
  • Molecular Sequence Data
  • Mutation*
  • Polymerase Chain Reaction
  • Proto-Oncogenes / genetics*
  • Receptor, Angiotensin, Type 1 / chemistry
  • Receptor, Angiotensin, Type 1 / genetics*
  • Receptor, Angiotensin, Type 1 / metabolism*
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism*
  • Transfection


  • Fluoresceins
  • Fluorescent Dyes
  • Indoles
  • Inositol Phosphates
  • Receptor, Angiotensin, Type 1
  • Receptors, G-Protein-Coupled
  • Angiotensin II
  • DAPI