RGD Reference Report - Pleiotropic AT1 receptor signaling pathways mediating physiological and pathogenic actions of angiotensin II. - Rat Genome Database

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Pleiotropic AT1 receptor signaling pathways mediating physiological and pathogenic actions of angiotensin II.

Authors: Hunyady, L  Catt, KJ 
Citation: Hunyady L and Catt KJ, Mol Endocrinol. 2006 May;20(5):953-70. Epub 2005 Sep 1.
RGD ID: 1581847
Pubmed: (View Article at PubMed) PMID:16141358
DOI: Full-text: DOI:10.1210/me.2004-0536

Angiotensin II (Ang II) activates a wide spectrum of signaling responses via the AT1 receptor (AT1R) that mediate its physiological control of blood pressure, thirst, and sodium balance and its diverse pathological actions in cardiovascular, renal, and other cell types. Ang II-induced AT1R activation via Gq/11 stimulates phospholipases A2, C, and D, and activates inositol trisphosphate/Ca2+ signaling, protein kinase C isoforms, and MAPKs, as well as several tyrosine kinases (Pyk2, Src, Tyk2, FAK), scaffold proteins (G protein-coupled receptor kinase-interacting protein 1, p130Cas, paxillin, vinculin), receptor tyrosine kinases, and the nuclear factor-kappaB pathway. The AT1R also signals via Gi/o and G11/12 and stimulates G protein-independent signaling pathways, such as beta-arrestin-mediated MAPK activation and the Jak/STAT. Alterations in homo- or heterodimerization of the AT1R may also contribute to its pathophysiological roles. Many of the deleterious actions of AT1R activation are initiated by locally generated, rather than circulating, Ang II and are concomitant with the harmful effects of aldosterone in the cardiovascular system. AT1R-mediated overproduction of reactive oxygen species has potent growth-promoting, proinflammatory, and profibrotic actions by exerting positive feedback effects that amplify its signaling in cardiovascular cells, leukocytes, and monocytes. In addition to its roles in cardiovascular and renal disease, agonist-induced activation of the AT1R also participates in the development of metabolic diseases and promotes tumor progression and metastasis through its growth-promoting and proangiogenic activities. The recognition of Ang II's pathogenic actions is leading to novel clinical applications of angiotensin-converting enzyme inhibitors and AT1R antagonists, in addition to their established therapeutic actions in essential hypertension.



Molecular Pathway Annotations    
Objects Annotated

Genes (Rattus norvegicus)
Agt  (angiotensinogen)
Agtr1a  (angiotensin II receptor, type 1a)
Agtr1b  (angiotensin II receptor, type 1b)
Gna11  (G protein subunit alpha 11)
Gnaq  (G protein subunit alpha q)

Genes (Mus musculus)
Agt  (angiotensinogen (serpin peptidase inhibitor, clade A, member 8))
Agtr1a  (angiotensin II receptor, type 1a)
Agtr1b  (angiotensin II receptor, type 1b)
Gna11  (guanine nucleotide binding protein, alpha 11)
Gnaq  (guanine nucleotide binding protein, alpha q polypeptide)

Genes (Homo sapiens)
AGT  (angiotensinogen)
AGTR1  (angiotensin II receptor type 1)
GNA11  (G protein subunit alpha 11)
GNAQ  (G protein subunit alpha q)


Additional Information