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Proceedings of the Symposium ‘Angiotensin AT 1 Receptors: From Molecular Physiology to Therapeutics’: MOLECULAR MECHANISMS OF ANGIOTENSIN II (AT 1a ) RECEPTOR ENDOCYTOSIS
Author(s) -
Thomas Walter G,
Thekkumkara Thomas J,
Baker Kenneth M
Publication year - 1996
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1996.tb02817.x
Subject(s) - endocytosis , internalization , angiotensin ii , receptor , microbiology and biotechnology , receptor mediated endocytosis , angiotensin ii receptor type 1 , g protein coupled receptor , biology , enzyme linked receptor , biochemistry , chemistry
SUMMARY1 Angiotensin II (AngII) initiates a variety of cellular responses through activation of type 1 (AT 1 ; with subtypes AT 1a and AT 1b ) and type 2 (AT 2 ) cell surface angiotensin receptors. Both AT 1 and AT 2 receptors couple to heterotrimeric guanyl nucleotide binding proteins (G‐proteins) and generate intracellular signals following recognition of extracellular AngII, but only AT 1 is targeted for the rapid ligand‐stimulated endocytosis (internalization) typical of many plasma membrane receptors. 2 AT 1 endocytosis proceeds through clathrin‐coated pits and is independent of G‐protein coupling which predicts that the AngII‐AT 1 receptor complex attains a conformation necessary for interaction with the endocytotic machinery, but separate from receptor signalling activation. 3 The function of AT 1 endocytosis and the reason for the disparity between AT 1 and AT 2 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 AT 1a 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 AT 1a receptor endocytosis.