RGD Reference Report - A novel angiotensin II type 2 receptor signaling pathway: possible role in cardiac hypertrophy. - Rat Genome Database

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A novel angiotensin II type 2 receptor signaling pathway: possible role in cardiac hypertrophy.

Authors: Senbonmatsu, T  Saito, T  Landon, EJ  Watanabe, O  Price E, JR  Roberts, RL  Imboden, H  Fitzgerald, TG  Gaffney, FA  Inagami, T 
Citation: Senbonmatsu T, etal., EMBO J. 2003 Dec 15;22(24):6471-82.
RGD ID: 1566502
Pubmed: (View Article at PubMed) PMID:14657020
DOI: Full-text: DOI:10.1093/emboj/cdg637

We describe a novel signaling mechanism mediated by the G-protein-coupled receptor (GPCR) angiotensin II (Ang II) type 2 receptor (AT(2)). Yeast two-hybrid studies and affinity column binding assay show that the isolated AT(2) C-terminus binds to the transcription factor promyelocytic zinc finger protein (PLZF). Cellular studies employing confocal microscopy show that Ang II stimulation induces cytosolic PLZF to co-localize with AT(2) at the plasma membrane, then drives AT(2) and PLZF to internalize. PLZF slowly emerges in the nucleus whereas AT(2) accumulates in the perinuclear region. Nuclear PLZF binds to a consensus sequence of the phosphatidylinositol-3 kinase p85 alpha subunit (p85 alpha PI3K) gene. AT(2) enhances expression of p85 alpha PI3K followed by enhanced p70(S6) kinase, essential to protein synthesis. An inactive mutant of PLZF abolishes this effect. PLZF is expressed robustly in the heart in contrast to many other tissues. This cardiac selective pathway involving AT(2), PLZF and p85 alpha PI3K may explain the absence of a cardiac hypertrophic response in AT(2) gene-deleted mice.

Annotation

Gene Ontology Annotations    

Biological Process

Cellular Component

Molecular Function

Molecular Pathway Annotations    
Objects Annotated

Genes (Rattus norvegicus)
Agtr2  (angiotensin II receptor, type 2)
Zbtb16  (zinc finger and BTB domain containing 16)

Genes (Mus musculus)
Agtr2  (angiotensin II receptor, type 2)

Genes (Homo sapiens)
AGTR2  (angiotensin II receptor type 2)


Additional Information