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AT 1 Receptor‐Mediated Nuclear Translocation of Raf‐1 in Brain Neurons
Author(s) -
Lu Di,
Yang Hong,
Raizada Mohan K.
Publication year - 1998
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1998.70010424.x
Subject(s) - nucleus , chromosomal translocation , microbiology and biotechnology , mapk/erk pathway , receptor , cytoplasm , cell nucleus , angiotensin ii , biology , losartan , kinase , nucleolus , signal transduction , chemistry , medicine , biochemistry , gene
Angiotensin II (Ang II) interacts with the neuronal AT 1 receptor subtype and initiates a cascade of signaling events involving activation of Ras‐Raf‐1‐MAP kinase. Raf‐1‐dependent activation of mitogen‐activated protein kinase (MAPK) is the key in the chronic norepinephrine neuromodulatory actions of Ang II and is associated with the translocation of MAPK into the nucleus. In view of these observations, this study was designed to determine if Ang II causes cellular redistribution of Raf‐1 in neuronal cells. Most of Raf‐1 was localized in the cytoplasmic compartment in neurons. Ang II treatment resulted in a time‐dependent increase in the translocation of immunoreactive Raf‐1 from the cytoplasm into the nucleus. A fourfold increase was observed in 15 min. The nuclear sequestration of Raf‐1 was blocked by losartan, an AT 1 receptor‐specific antagonist, and not by PD123319, an AT 2 receptor‐specific antagonist. Confocal microscopic analysis of immunofluorescence data confirmed the nuclear translocation and further showed that Raf‐1 was exclusively localized into the nucleolus. These observations demonstrate, for the first time, that Ang II stimulates Raf‐1 targeting into the neuronal nucleus, and they suggest that this translocation may play a direct role in the transcriptional regulation of Ang II actions.