Linked Life Data

7989302

Source:http://linkedlifedata.com/resource/pubmed/id/7989302

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
50
pubmed:dateCreated
1995-1-12
pubmed:abstractText
The type 1 angiotensin II (AT1) receptor undergoes rapid endocytosis and down-regulation after agonist binding. In studies on the structural determinants of agonist-induced endocytosis, serial deletions in the cytoplasmic tail of the rat AT1a receptor showed that the carboxyl-terminal 22 amino acids are not necessary for its internalization. However, internalization was markedly impaired by the removal of one additional amino acid (Leu337) and was reduced by 95% after removal of Ser335 and Thr336. Single alanine replacements of amino acids in this region showed that individual substitutions of Thr332, Ser335, Thr336, Leu337, and Ser338 caused moderate but significant impairment of the internalization rate. Replacement of both Ser335 and Thr336 with alanine residues further impaired the internalization rate, and triple alanine replacement of the Ser-Thr-Leu motif reduced internalization to almost the same extent as the corresponding tail deletion mutant. The Ser-Thr-Leu motif is highly conserved in mammalian AT1 receptors but is not present in the noninternalizing type 2 angiotensin II receptor. These data demonstrate that a serine/threonine-rich region including Leu337 in the cytoplasmic tail of the AT1 receptor is a major requirement for endocytosis of the hormone-receptor complex and support the concept that similar motifs in other G protein-coupled receptors are determinants of their agonist-induced internalization.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
16
pubmed:volume
269
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
31378-82
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Identification of a cytoplasmic Ser-Thr-Leu motif that determines agonist-induced internalization of the AT1 angiotensin receptor.
pubmed:affiliation
Endocrinology and Reproduction Research Branch, NICHD, National Institutes of Health, Bethesda, Maryland 20892.
pubmed:publicationType
Journal Article