Biomaterial Database

Molecular mechanisms of angiotensin II (AT1A) receptor endocytosis. 1996

W G Thomas, and T J Thekkumkara, and K M Baker

Weis Center for Research, Geisinger Clinic, Danville, Pennsylvania, USA.

1. Angiotensin II (AngII) initiates a variety of cellular responses through activation of type 1 (AT1; with subtypes AT1A and AT1B) and type 2 (AT2) cell surface angiotensin receptors. Both AT1 and AT2 receptors couple to heterotrimeric guanyl nucleotide binding proteins (G-proteins) and generate intracellular signals following recognition of extracellular AngII, but only AT1 is targeted for the rapid ligand-stimulated endocytosis (internalization) typical of many plasma membrane receptors. 2. AT1 endocytosis proceeds through clathrin-coated pits and is independent of G-protein coupling which predicts that the AngII-AT1 receptor complex attains a conformation necessary for interaction with the endocytotic machinery, but separate from receptor signalling activation. 3. The function of AT1 endocytosis and the reason for the disparity between AT1 and AT2 endocytosis is not fully appreciated, but the latter probably reflects differences in the primary amino acid sequence of these two receptor types. 4. For many receptors that undergo internalization, it has been established that internalization motifs (2-6 amino acids, often incorporating crucial tyrosine and hydrophobic amino acids) within the cytoplasmic regions of the receptor mediate the selective recruitment of activated receptors into clathrin-coated pits and vesicles. 5. Mutagenesis studies on the AT1A receptor, aimed at identifying such motifs, reveal that sites within the third cytoplasmic loop and the cytoplasmic carboxyl terminal region are important for AngII-stimulated AT1A receptor endocytosis.

UI	MeSH Term	Description	Entries
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D011945	Receptors, Angiotensin	Cell surface proteins that bind ANGIOTENSINS and trigger intracellular changes influencing the behavior of cells.	Angiotensin Receptor,Angiotensin Receptors,Angiotensin II Receptor,Angiotensin III Receptor,Receptor, Angiotensin II,Receptor, Angiotensin III,Receptor, Angiotensin
D002462	Cell Membrane	The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.	Plasma Membrane,Cytoplasmic Membrane,Cell Membranes,Cytoplasmic Membranes,Membrane, Cell,Membrane, Cytoplasmic,Membrane, Plasma,Membranes, Cell,Membranes, Cytoplasmic,Membranes, Plasma,Plasma Membranes
D002966	Clathrin	The main structural coat protein of COATED VESICLES which play a key role in the intracellular transport between membranous organelles. Each molecule of clathrin consists of three light chains (CLATHRIN LIGHT CHAINS) and three heavy chains (CLATHRIN HEAVY CHAINS) that form a structure called a triskelion. Clathrin also interacts with cytoskeletal proteins.
D003034	Coated Pits, Cell-Membrane	Specialized regions of the cell membrane composed of pits coated with a bristle covering made of the protein CLATHRIN. These pits are the entry route for macromolecules bound by cell surface receptors. The pits are then internalized into the cytoplasm to form the COATED VESICLES.	Bristle-Coated Pits,Cell-Membrane Coated Pits,Bristle Coated Pits,Bristle-Coated Pit,Cell Membrane Coated Pits,Cell-Membrane Coated Pit,Coated Pit, Cell-Membrane,Coated Pits, Cell Membrane,Pit, Bristle-Coated,Pit, Cell-Membrane Coated,Pits, Bristle-Coated,Pits, Cell-Membrane Coated
D004705	Endocytosis	Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. ENDOSOMES play a central role in endocytosis.	Endocytoses
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000595	Amino Acid Sequence	The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.	Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D000804	Angiotensin II	An octapeptide that is a potent but labile vasoconstrictor. It is produced from angiotensin I after the removal of two amino acids at the C-terminal by ANGIOTENSIN CONVERTING ENZYME. The amino acid in position 5 varies in different species. To block VASOCONSTRICTION and HYPERTENSION effect of angiotensin II, patients are often treated with ACE INHIBITORS or with ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKERS.	Angiotensin II, Ile(5)-,Angiotensin II, Val(5)-,5-L-Isoleucine Angiotensin II,ANG-(1-8)Octapeptide,Angiotensin II, Isoleucine(5)-,Angiotensin II, Valine(5)-,Angiotensin-(1-8) Octapeptide,Isoleucine(5)-Angiotensin,Isoleucyl(5)-Angiotensin II,Valyl(5)-Angiotensin II,5 L Isoleucine Angiotensin II,Angiotensin II, 5-L-Isoleucine
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia