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

Autor: Edward Price, Takako Saito, Tadashi Inagami, Richard L. Roberts, Hans Imboden, F. Andrew Gaffney, Erwin J. Landon, Otsu Watanabe, Trinita G. Fitzgerald, Takaaki Senbonmatsu
Rok vydání: 2003
Předmět:
endocrine system
Molecular Sequence Data
Kruppel-Like Transcription Factors
Cardiomegaly
CHO Cells
Biology
Transfection
Receptor
Angiotensin
Type 2
General Biochemistry
Genetics and Molecular Biology
Mice
Phosphatidylinositol 3-Kinases
Cricetinae
Escherichia coli
Animals
Humans
Promyelocytic Leukemia Zinc Finger Protein
Amino Acid Sequence
Cloning
Molecular
Receptor
Molecular Biology
Transcription factor
Conserved Sequence
PI3K/AKT/mTOR pathway
G protein-coupled receptor
Mice
Knockout
Zinc finger
Sequence Homology
Amino Acid
General Immunology and Microbiology
Kinase
Ribosomal Protein S6 Kinases
General Neuroscience
Heart
Zinc Fingers
Articles
Molecular biology
Angiotensin II
Rats
DNA-Binding Proteins
Protein Transport
cardiovascular system
Signal transduction
Sequence Alignment
hormones
hormone substitutes
and hormone antagonists
Signal Transduction
Transcription Factors
Zdroj: The EMBO Journal. 22:6471-6482
ISSN: 1460-2075
DOI: 10.1093/emboj/cdg637
Popis: 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.
Databáze: OpenAIRE
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