The scaffold protein CNK1 interacts with the angiotensin II type 2 receptor.
The scaffold protein CNK1 mediates proliferative as well as antiproliferative responses including differentiation and apoptosis. The angiotensin II type 2 (AT2) receptor belongs to the class of G protein-coupled receptors and also promotes antiproliferative effects. Here we report that CNK1 binds through the sterile alpha motif (SAM) and the conserved region in CNK (CRIC) to the AT2 receptor. The exchange of a conserved leucine residue with arginine in the CRIC domain increases the binding affinity of CNK1 to the AT2 receptor. The insertion of a negatively charged amino acid stretch into the linker region between the N- and the C-terminal part of CNK1 strengthens the interaction between CNK1 and the AT2 receptor in a Ras-regulated manner. The biological significance of the interaction was supported by coprecipitation of CNK1 and the AT2 receptor in mouse heart extracts. Thus, CNK1 may play a role in the AT2 receptor-mediated signaling pathways.
Fritz
Rafael D
RD
Institute of Medical Virology, University of Zurich, 8006 Zurich, Switzerland.
Radziwill
Gerald
G
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001120:Arginine / Q000502:physiology; D002460:Cell Line; D029721:Drosophila Proteins / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007930:Leucine / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000502:physiology; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism*; D016415:Sequence Alignment
D048868:Adaptor Proteins, Signal Transducing; C115753:CNK protein, Drosophila; C500833:CNKSR1 protein, human; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D044139:Receptor, Angiotensin, Type 2; D001120:Arginine; D007930:Leucine