Cloning and characterization of ATRAP, a novel protein that interacts with the angiotensin II type 1 receptor.
The carboxyl-terminal cytoplasmic domain of the angiotensin II type 1 (AT1) receptor has recently been shown to interact with several classes of cytoplasmic proteins that regulate different aspects of AT1 receptor physiology. Employing yeast two-hybrid screening of a mouse kidney cDNA library with the carboxyl-terminal cytoplasmic domain of the murine ... AT1a receptor as a bait, we have isolated a novel protein with a predicted molecular mass of 18 kDa, which we have named ATRAP (for AT1 receptor-associated protein). ATRAP interacts specifically with the carboxyl-terminal domain of the AT1a receptor but not with those of angiotensin II type 2 (AT2), m3 muscarinic acetylcholine, bradykinin B2, endothelin B, and beta2-adrenergic receptors. The mRNA of ATRAP was abundantly expressed in kidney, heart, and testis but was poorly expressed in lung, liver, spleen, and brain. The ATRAP-AT1a receptor association was confirmed by affinity chromatography, by specific co-immunoprecipitation of the two proteins, and by fluorescence microscopy, showing co-localization of these proteins in intact cells. Overexpression of ATRAP in COS-7 cells caused a marked inhibition of AT1a receptor-mediated activation of phospholipase C without affecting m3 receptor-mediated activation. In conclusion, we have isolated a novel protein that interacts specifically with the carboxyl-terminal cytoplasmic domain of the AT1a receptor and affects AT1a receptor signaling.
Mesh Terms:
1-Sarcosine-8-Isoleucine Angiotensin II, Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Angiotensin II, Animals, Base Sequence, Carrier Proteins, Cloning, Molecular, DNA, Complementary, Dose-Response Relationship, Drug, Enzyme Activation, Mice, Molecular Sequence Data, Protein Binding, Receptor, Angiotensin, Type 1, Receptor, Angiotensin, Type 2, Receptors, Angiotensin, Recombinant Proteins, Saccharomyces cerevisiae, Tissue Distribution, Type C Phospholipases
1-Sarcosine-8-Isoleucine Angiotensin II, Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Angiotensin II, Animals, Base Sequence, Carrier Proteins, Cloning, Molecular, DNA, Complementary, Dose-Response Relationship, Drug, Enzyme Activation, Mice, Molecular Sequence Data, Protein Binding, Receptor, Angiotensin, Type 1, Receptor, Angiotensin, Type 2, Receptors, Angiotensin, Recombinant Proteins, Saccharomyces cerevisiae, Tissue Distribution, Type C Phospholipases
J. Biol. Chem.
Date: Jun. 11, 1999
PubMed ID: 10358057
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