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Titolo:
DEPENDENCE OF AGONIST ACTIVATION ON A CONSERVED APOLAR RESIDUE IN THE3RD INTRACELLULAR LOOP OF THE AT(1) ANGIOTENSIN RECEPTOR
Autore:
HUNYADY L; ZHANG M; JAGADEESH G; BOR M; BALLA T; CATT KJ;
Indirizzi:
NIH,ENDOCRINOL & REPROD RES BRANCH,NICHHD,BLDG 10 BETHESDA MD 20892 NIH,ENDOCRINOL & REPROD RES BRANCH,NICHHD BETHESDA MD 20892 US FDA,DIV CARDIO RENAL DRUG PROD,CTR DRUG EVALUAT & RES ROCKVILLE MD20857
Titolo Testata:
Proceedings of the National Academy of Sciences of the United Statesof America
fascicolo: 19, volume: 93, anno: 1996,
pagine: 10040 - 10045
SICI:
0027-8424(1996)93:19<10040:DOAAOA>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
BETA-ADRENERGIC-RECEPTOR; ADRENAL GLOMERULOSA CELLS; PROTEIN-COUPLED RECEPTORS; SMOOTH-MUSCLE CELLS; II RECEPTOR; INDUCED INTERNALIZATION; SIGNAL-TRANSDUCTION; ALDOSTERONE SECRETION; POTENTIAL MECHANISM; TYROSINE RESIDUE;
Keywords:
G PROTEIN-COUPLED RECEPTORS; INOSITOL PHOSPHATE SIGNALING; RECEPTOR INTERNALIZATION; SITE-DIRECTED MUTAGENESIS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
54
Recensione:
Indirizzi per estratti:
Citazione:
L. Hunyady et al., "DEPENDENCE OF AGONIST ACTIVATION ON A CONSERVED APOLAR RESIDUE IN THE3RD INTRACELLULAR LOOP OF THE AT(1) ANGIOTENSIN RECEPTOR", Proceedings of the National Academy of Sciences of the United Statesof America, 93(19), 1996, pp. 10040-10045

Abstract

The coupling of agonist-activated seven transmembrane domain receptors to G proteins is known to involve the amino-terminal region of theirthird cytoplasmic loop. Analysis of the amino acids in this region ofthe rat type 1a angiotensin (AT(1a)) receptor identified Leu-222 as an essential residue in receptor activation by the physiological agonist, angiotensin II (Ang II). Nonpolar replacements for Leu-222 yielded functionally intact AT(1) receptors, while polar or charged residues caused progressive impairment of Ang II-induced inositol phosphate generation. The decrease in agonist-induced signal generation was associated with a parallel reduction of receptor internalization, and was mostpronounced for the Lys-222 mutant receptor. Although this mutant showed normal binding of the peptide antagonist, [Sar(1),Ile(8)]Ang II, its affinity for Ang II was markedly reduced, consistent with its inability to adopt the high-affinity conformation. A search revealed that many G(q)-coupled receptors contain an apolar amino acid (frequently leucine) in the position corresponding to Leu-222 of the AT(1) receptor. These findings suggest that such a conserved apolar residue in the third intracellular loop is a crucial element in the agonist-induced activation of the AT(1) and possibly many other G protein-coupled receptors.

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Documento generato il 03/04/20 alle ore 10:02:22